Symptoms and General Pathology

All Conditions

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Blood and Lymph Conditions

Immune System Diseases

Infections

Rare Diseases

Syndrome

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Mycoses

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Hodgkin Disease

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Lymphoma, T-Cell, Cutaneous

Sezary Syndrome

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Lymphomatoid Papulosis

Neoplasms by Histologic Type

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Communicable Diseases

Bacterial Infections

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Anaplastic Large Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Fludarabine

Fludarabine phosphate

Bendamustine Hydrochloride

Antineoplastic Agents, Alkylating

Alkylating Agents

A 3+3 design in adult subjects. Subjects in the first dose level will receive ATLCAR.CD30.CCR4 cells alone, once safety has been established, the initial dose of ATLCAR.CD30.CCR4 will be combined with a fixed dose of ATLCAR.CD30 cells in the next dose level. Every time the dose of ATLCAR.CD30.CCR4 is escalated, subjects in that dose level will receive ATLCAR.CD30.CCR4 alone prior to subsequent dose level enrolling subjects to receive a combination of fixed dose ATLCAR.CD30 and the selected dose level of ATLCAR.CD30.CCR4. The six dose levels will consist of: dose level 1 = 2 × 10\^7 ATLCAR.CD30.CCR4 cells/m2; dose level 2 = 1 × 10\^8 ATLCAR.CD30 cells/m2 and 2 × 10\^7 ATLCAR.CD30.CCR4 cells/m2; dose level 3 = 5 × 10\^7/m2 ATLCAR.CD30.CCR4 cells/m2; dose level 4 = 1 × 10\^8 ATLCAR.CD30 cells/m2 and 5 × 10\^7 ATLCAR.CD30.CCR4 cells/m2; dose level 5 = 1 × 10\^8/m2 ATLCAR.CD30.CCR4 cells/m2; dose level 6 = 1 × 108 ATLCAR.CD30 cells/m2 and 1 × 108 ATLCAR.CD30.CCR4 cells/m2.

Three dose levels are being evaluated: 2x10\^7, 5x10\^7, 1x10\^8

ATLCAR.CD30.CCR4 cells

ALTCAR.CD30 cells

70 mg/m\^2/day Bendamustine for 3 days for lymphodepletion prior to cell infusion

Bendamustine

30 mg/m\^2/day Fludarabine for 3 days for lymphodepletion prior to cell infusion

Catherine Cheng

Caroline Babinec

Natalie Grover, MD

The body has different ways of fighting infection and disease. No single way is perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with bacteria or viruses. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to treat cancer. This study will combine both T cells and antibodies in order to create a more effective treatment called Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen (ATLCAR.CD30). Another treatment being tested includes the Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen with CCR4 (ATLCAR.CD30.CCR4) to help the cells move to regions in the patient's body where the cancer is present. Participants in this study will receive either ATLCAR.CD30.CCR4 cells alone or will receive ATLCAR.CD30.CCR4 cells combined with ATLCAR.CD30 cells.

Previous studies have shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. The new gene that is put in the T cells in this study makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric (combination) receptor-activated T cells (ATLCAR.CD30) can kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown.

Researchers are working to identify ways to improve the ability of ATLCAR.CD30 to destroy tumor cells. T cells naturally produce a protein called CCR4 which functions as a navigation system directing T cells toward tumor cells specifically. In this study, researchers will also genetically modify ATLCAR.CD30 cells to produce more CCR4 proteins and they will be called ATLCAR.CD30.CCR4. The study team believes that the ATLCAR.CD30.CCR4 cells will be guided directly toward the tumor cells based on their navigation system. In addition, the study team believes the majority of ATLCAR.CD30 cells will also be guided directly toward tumor cells when given together with ATLCAR.CD30.CCR4, increasing their anti-cancer fighting ability.

This is the first time ATLCAR\>CD30.CCR4 cells or combination of ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells are used to treat lymphoma. The purpose of this study to determine the following:

* What is the safe dose of ATLCAR.CD30.CCR4 cells to give to patients
* What is the safe dose of the combination of ATLCAR.CD30 and ATLCAR.CD30.CCR4 cells to give to patients

This study is a single center, open-label Phase I clinical trial designed to determine the safety of escalating doses of autologous activated T lymphocytes (ATLs) co-expressing the chimeric antigen receptor specific for the CD30 antigen and the CCR4 chemokine receptor (ATLCAR.CD30.CCR4) in subjects with relapsed/refractory CD30+ Hodgkin (HL) and cutaneous T Cell Lymphoma (CTCL). Subjects with grey zone lymphoma will also be eligible to enroll on this protocol; the characteristics of grey zone lymphoma are very similar to HL and therefore will be referred to collectively throughout the protocol under the general term of HL. Subjects will receive either ATLCAR.CD30.CCR4 or the ATLCAR.CD30.CCR4 product in combination with an ATL product encoding only the CAR.CD30 (ATLCAR.CD30). The dose for ATLCAR.CD30 will be fixed at the highest dose level as this product has been shown to be safe in phase I trials with and without lymphodepletion. Six total dose levels of ATLCAR.CD30.CCR4 with or without ATLCAR.CD30 will be tested. Prior to receiving the infusions, subjects will undergo lymphodepletion with bendamustine and fludarabine, The 3+3 design will be used for estimating the maximum tolerated dose (MTD) of ATLCAR.CD30.CCR4 in combination with ATLCAR.CD30. Any dose level may be expanded to 4-9 subjects to explore adverse events (AEs) of special interest prior to moving to the next dose level. If due to the expansion ≥1/3 of the total number of subject on that dose level experiences a DLT, the study would not escalate to the next highest dose level and the maximum tolerated dose would be exceeded. The final MTD will be the highest dose of ATLCAR.CD30.CCR4 and ATLCAR.CD30 with observed DLT rate of less than 1/3. An expansion cohort will enroll up to 8 subjects at the MTD of ATLCAR.CD30.CCR4 and ATLCAR.CD30 to further assess safety and efficacy of these cellular products. Secondary endpoints include evaluation of persistence of ATLCAR.CD30.CCR4 vs. ATLCAR.CD30 in the peripheral blood, accumulation of ATLCAR.CD30.CCR4 vs. ATLCAR.CD30 in tumor biopsies, and progression free survival (PFS).

LCCC1606-ATL builds on LCCC1532-ATL, a phase Ib/II trial investigating the safety and efficacy of ATLCAR.CD30 in subjects with CD30+ lymphoma.

OUTLINE

Cell Procurement

Up to 300 mL total of peripheral blood will be obtained (in up to 3 collections) from subjects for cell procurement. Up to 300 mL total of peripheral blood will be obtained (in up to 3 collections) from subjects for cell procurement. Additionally, leukapheresis may be performed to isolate sufficient cells in subjects with a low absolute lymphocyte count or who had inadequate peripheral blood collection. The parameters for apheresis will be up to 2 blood volumes. Collected peripheral blood may be used for generation of CAR-T cells if the cells were collected on another CAR-T cell trial for which Lineberger Comprehensive Cancer Center is the sponsor and if the subject is eligible for procurement/screening on the LCCC 1606-ATL protocol. ATLCAR.CD30 cells manufactured for a different protocol may be used for LCCC 1606-ATL, if they fit specifications for the protocol and the patient qualifies for the protocol.

Lymphodepletion Regimen

In order to receive lymphodepletion and CAR-T cells, subjects must still have evidence of active disease.

All subjects will receive lymphodepletion with bendamustine 70 mg/m2 and fludarabine 30 mg/m2 for 3 days to reduce possible toxicity associated with the agent prior to administration of CAR-T cells.

NOTE: Any subject who tests positive for Hepatitis B core antibody and negative for Hepatitis B viral load during screening must initiate an anti-Hepatitis B prophylaxis regimen prior to lymphodepletion.

Bendamustine and fludarabine will be administered concomitantly for lymphodepletion (i.e., intravenous (IV) administration of bendamustine 70 mg/m2/day over 3 consecutive days and IV fludarabine 30 mg/m2/day over 3 consecutive days) prior to the first CAR-T cell infusion. Bendamustine should be administered first followed by IV administration of fludarabine.

Cell Administration

ATLCAR.CD30.CCR4 with or without ATLCAR.CD30 cells will be given to eligible subjects 2-14 days (preferably 2-4 days) after lymphodepletion with fludarabine and bendamustine. The dose of cells will vary, depending on the cohort enrolled. The cells will be administered by a licensed provider (oncology nurse or physician) via intravenous injection over 1-10 minutes through either a peripheral or a central line. The expected volume will be 1-50cc. Subjects in the dose expansion part of the study who received the highest safe dose level of ATLCAR.CD30 and ATLCAR.CD30.CCR4 may receive a second infusion of ATLCAR.CD30 and ATLCAR.CD30.CCR4 if cells are available equal to the dose administered for the first cell infusion (or a lower dose).

Duration of Therapy

Therapy in LCCC1606-ATL involves one to two infusion(s) of ATLCAR.CD30.CCR4 with or without ATLCAR.CD30 cells. Treatment with one infusion will be administered unless:

* Subject decides to withdraw from study treatment, OR
* General or specific changes in the subject's condition render the subject unacceptable for further treatment in the judgment of the investigator.

Duration of Follow-up

Subjects who receive a cell infusion will be followed for up to 15 years for replication competent retrovirus (RCR) evaluation or until death, whichever occurs first. Subjects who are removed from study and do not receive the cellular therapy product due to unacceptable adverse events will be followed until resolution or stabilization of the adverse event. Subjects who have progressive disease or initiate another cancer therapy after receiving a cell infusion(s) will still be required to complete abbreviated follow up procedures.

Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and CTCL

Phase I Study of the Administration of T Lymphocytes Co-Expressing the CD30 Chimeric Antigen Receptor (CAR) and CCR4 for Relapsed/Refractory CD30+ Hodgkin Lymphoma and Cutaneous T-Cell Lymphoma

Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0), CRS toxicity will be graded according to the toxicity scale outlined in CRS Grading Criteria/Link to CRS Management Guidelines and ICANS will be graded according to the toxicity scale outlined in Management of Neurotoxicity/Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) from CAR-T Therapy. The MTD will be based on the rate of dose-limiting toxicity.

PFS is defined from day of ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 infusion to relapse (in subjects in a documented complete response prior to conditioning chemotherapy) or progression (in subjects not in a complete response prior to conditioning chemotherapy), or death as a result of any cause

Overall survival will be measured from the date of administration of ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 infusion to date of death

The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) by 7 weeks post ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 infusion

Differential infiltration of ATLCAR.CD30.CCR4 vs. ATLCAR.CD30 cells in tumor biopsies in subjects receiving both ATLCAR.CD30.CCR4 and ATLCAR.CD30 cellular products will be determined by measuring the level of the transgene and by phenotypic analyses

Persistence of ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells in peripheral blood will be determined by quantitative polymerase chain reaction (PCR) and flow cytometry in samples of peripheral blood in subjects who received infusion of both ATLCAR.CD30.CCR4 and ATLCAR.CD30 cellular products

University Cancer Research Fund at Lineberger Comprehensive Cancer Center

Stand Up To Cancer

UNC Lineberger Comprehensive Cancer Center

Leukemia

The trial will be conducted in a manner of simon two-stage design with Anti-CD30-CAR-transduced T cells, beginning in the first stage with the aim of over 30% reaction rate among 15 patients with B cell malignancies. Only when the expected reaction rate is achieved the 30 patients left can be recruited.

The first 3 enrolled patients will receive autologous-derived CD30-targeted CAR-T cells on day 1, 2 and 3 with respective 10%, 30% and 60% of the total expected dosage after receiving lymphodepleting chemotherapy. If the 3 patients don't display severe toxicity, the next patients enrolled will get infused in 2 days with respective 40% and 60% total dosage.

Anti-CD30-CAR-transduced T cells

Cheng Qian, MD, PhD

Shiqi Li, MD

Cheng Qian, PhD

Zhi Yang, PhD

The overall purpose of this study is to explore the therapeutic effect of BCMA-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of lymphocyte derived malignancies.

CD30 is originally described as a marker of Hodgkin's and Reed-Sternberg cells in Hodgkin's lymphoma. CD30 antibody has been applied to treat lymphocyte derived malignancies. To explore the potency of CD30 in CAR-T therapy, this trial is designed and conducted to test the safety and effect of CD30-targeted CAR-T.

A Clinical Research of CD30-Targeted CAR-T in Lymphocyte Malignancies

Determine the toxicity profile of the BCMA targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

Southwest Hospital, China

Principal Investigator of Biotherapy Center

Cicatrix

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, B-Cell

Hematologic Diseases

Chronic Lymphocytic Leukemia

Patients who have relapsed and refractory B cell malignancies after chemotherapy will be treated with CD19 and CD20/CD22/CD30/CD38/CD70/CD123-specific gene-engineered T cells.

4SCAR19 and 4SCAR22

4SCAR19 and 4SCAR38

4SCAR19 and 4SCAR20

4SCAR19 and 4SCAR123

4SCAR19 and 4SCAR70

4SCAR19 and 4SCAR30

Lung-Ji Chang, PhD

Yuhua Li, M.D, Ph.D

Lihua Yang, M.D., Ph.D.

Xun Lai, MD

The study will evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 (4SCAR19) and CD20 (4SCAR20), CD22 (4SCAR22), CD30 (4SCAR30), CD38 (4SCAR38), CD70 (4SCAR70) or CD123 (4SCAR123) for patients with B cell malignancies. Clinical response and development of a standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.

Background:

T cells modified with lentiviral chimeric antigen receptor (CAR) gene have been studied in different clinical settings. Recent successes suggest that increased costimulatory signaling in the CAR design is critical for long term efficacy. Several clinical reports indicate that many patients still relapse and developed CD19-negative cancer cells after CD19 targeted therapy. Thus, to prevent the target escapes and improve the therapeutic effects, CAR gene-modified T cells targeting CD20, CD22, CD30, CD38, CD70 or CD123 are considered to apply together with CD19 CAR-T cells.

Activation of T cell response to high tumor burden may induce a severe response. To increase safety, a novel design using an inducible caspase 9 fusion gene has been incorporated in the CAR gene. A 4th generation CAR lentiviral vector (4SCAR) carrying multiple costimulatory signals for CD28/CD137/CD27 plus an inducible apoptotic caspase 9 gene has been established. This study aims to evaluate the activities of a combination of CAR gene-modified T cells to target cancer cells based on specific CD19/CD20/CD22/CD30/CD38/CD70/CD123 single chain antibody gene designs (4SCAR19/20/22/30/38/70/123).

Objective:

To evaluate safety and efficacy of administrating 4SCAR19, 4SCAR20, 4SCAR22, 4SCAR30, 4SCAR38, 4SCAR70 and 4SCAR123 T cells to patients with mixed CD19 positive and negative B cell malignancies following a cyclophosphamide/fludarabine based conditioning regimen.

Eligibility:

Patients older than 6-month-old with CD19 positive or negative B cell malignancies that have recurred after or refractory to standard therapy and is deemed incurable using standard treatment.

Design:

Participants will be screened based on cancer cell phenotype analyzed using flow cytometry or immunohistochemical staining methods. Peripheral blood mononuclear cells (PBMC) will be obtained through apheresis. On Day -5 to -7, T cells from PBMC will be activated and enriched, which will be followed by 4SCAR19, 4SCAR20, 4SCAR22, 4SCAR30, 4SCAR38, 4SCAR70 and 4SCAR123 lentiviral transduction. The total cell preparation time is approximately 5-7 days. Participants will receive a preparative conditioning regimen comprising cyclophosphamide/fludarabine to prepare their immune system to accommodate the modified CAR T cells. The preparative regimen will depend on the immune condition of patients, which is consistent with standard chemotherapy conditioning regimen. Participants will receive an infusion of the modified 4SCAR19 and 4SCAR20/22/30/38/70/123 T cells and closely followed up for treatment-related responses. Participants will be continuously monitored for CAR T cells and clinical responses in a preset timeline.

Combination CAR-T Cell Therapy Targeting Hematological Malignancies

Combination CAR-T Therapy of 4SCAR19 Plus 4SCAR20, 22, 38, 70 and 123 Targeting Hematological Malignancies

physiological parameter (for safety, measuring cytokine response, fever, symptoms)

scale of CAR copies and leukemic cell burden (for efficacy)

Shenzhen Geno-Immune Medical Institute

President

Antibodies

Immunomodulating Agents

Antibodies, Bispecific

Immunoglobulins

1.5 mg/kg of AFM13 once weekly for weeks 1-8.

7 mg/kg of AFM13 once weekly for weeks 1-8.

AFM13 is a recombinant antibody construct against human CD30 and CD16A. It will be given to patients intravenously at the dose and schedule applicable to the cohort the patient was enrolled in specified in the various arms listed.

AFM13

Ahmed Sawas, MD

The investigators plan to investigate AFM13 and evaluate its ability to facilitate and redirect the Natural Killer (NK) cells in eliminating CD30-positive lymphoma targets in the skin and, by inference, other organs involved by the lymphoma.

This is an open label, Phase Ib/IIa study designed to evaluate the biologic activity of AFM13 in patients with relapsed or refractory CD30-positive lymphomas with cutaneous involvement. Primary cutaneous CD30-positive lymphoproliferative disorders (LPD) represent a spectrum from lymphomatoid papulosis (LyP), to primary cutaneous anaplastic large cell lymphoma (C-ALCL), to transformed mycosis fungoides (TMF).

The most indolent form of primary cutaneous CD30-positive LPD is LyP, which is usually well controlled with low dose oral methotrexate, but control of the disease frequently requires life-long therapy. In contrast, TMF is an aggressive disease which does not have a standard of care, as patients are treated with various modalities of care with variable outcomes). The spectrum of other CD30-positive lymphomas with cutaneous presentation is very broad and involves systemic B and T cell lymphomas with various clinical behaviors.

Redirecting Natural Killer (NK) cells towards these CD30-positive malignancies through direct engagement with AFM13 is expected to induce tumor cell killing through NK cell-mediated and T cell-mediated cytotoxicity (i.e., cytotoxic T lymphocytes (CTL)).

The primary objective of this trial is to study the biologic and immunologic effects induced by the administration of various doses of AFM13, when given as a single agent.

AFM13 in Relapsed/Refractory Cutaneous Lymphomas

Clinical and Biological Evaluation of the Novel CD30/CD16A Tetravalent Bispecific Antibody (AFM13) in Relapsed or Refractory CD30-Positive Lymphoma With Cutaneous Presentation: A Biomarker Phase Ib/IIa Study

Incidence of Treatment-Emergent Adverse Events \[Safety and Toxicity\] broken down by adverse event and CTCAE v4.0 grade of each event.

The sum of patients with partial responses and complete responses.

Ahmed Sawas

Assistant Professor of Medicine

1.5 mg/kg of AFM13 once weekly for weeks 1-8.

AFM13: AFM13 is a recombinant antibody construct against human CD30 and CD16A. It will be given to patients intravenously at the dose and schedule applicable to the cohort the patient was enrolled in specified in the various arms listed.

Cohort 1

7.0 mg/kg of AFM13 once weekly for weeks 1-8.

AFM13: AFM13 is a recombinant antibody construct against human CD30 and CD16A. It will be given to patients intravenously at the dose and schedule applicable to the cohort the patient was enrolled in specified in the various arms listed.

Cohort 2

7.0 mg/kg CIVI of AFM13 once weekly for weeks 1-8.

AFM13: AFM13 is a recombinant antibody construct against human CD30 and CD16A. It will be given to patients intravenously at the dose and schedule applicable to the cohort the patient was enrolled in specified in the various arms listed.

Cohort 3

200 mg ( Flat dose) of AFM13 once weekly for weeks 1-8.

AFM13: AFM13 is a recombinant antibody construct against human CD30 and CD16A. It will be given to patients intravenously at the dose and schedule applicable to the cohort the patient was enrolled in specified in the various arms listed.

Cohort 4

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

Overall Response Rate (ORR)

Overall Study

Phase Ib: In adults, and separately, in children, two doses will be investigated 1x10\^8 cells/m2 and 2x10\^8 cells/m\^2. The study team will run two independent dose-escalation sequences, one for adults and another one for children. The study team plans to use the 3+3 design and start with a low dose of 1x10\^8 cells/m2. If there are no DLT in first 3 patients, the study team will go up to the dose of 2 x 10\^8 cells/m2. If there is toxicity in 1/3 patients in the initial cohort, the study team would expand to enroll up to 6 patients. If there are dose limiting toxicities (DLT) at the dose of 2 x 10\^8 cells/m\^2, the study team will initially decrease the dose to an intermediate dose of 1.5 x 10\^8 cells/m\^.

Phase II: The study team planning to enroll 31 patients to contribute data. Sequential boundary will be used to monitor DLT rate.

For Phase Ib, in adults and separately in children, two doses will be investigated: 1x10\^8 cells/m\^2 and 2x10\^8 cells/m\^2. Phase II patients will receive the dose level decided upon in Phase I.

ATLCAR.CD30 cells

Anne Beaven, MD

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study is designed to combine both T cells and antibodies to create a more effective treatment called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) administration.

In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. The new gene that is put in the T cells in this study makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown.

The purpose of this research study is to establish a safe dose of ATLCAR.CD30 cells to infuse after lymphodepleting chemotherapy and to estimate the number patients whose cancer does not progress for two years after ATLCAR.CD30 administration. This study will also look at other effects of ATLCAR.CD30 cells, including their effect on the patient's cancer.

STUDY OBJECTIVES

Primary Objective (Phase Ib portion of Study) To establish a safe dose (ie, number cells/m2) of ATLCAR.CD30 to infuse after lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

To establish a safe dose (ie, number cells/m2) of ATLCAR.CD30 to infuse after lymphodepletion with bendamustine and fludarabine in pediatric patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

Primary Objective (Phase II portion of study) To estimate 2 year progression free survival (PFS) after administration of ATLCAR.CD30 in combined adult/pediatric patients with CD30+ refractory/relapsed HL and NHL

Secondary Objectives

To estimate 2 year overall survival (OS) after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine in adult patients with CD30+ relapsed/refractory HL and NHL.

To estimate 2 year OS after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.

To estimate 2 year PFS after administration of ATLCAR.CD30 following lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed HL and NHL.

To estimate 2 year PFS after administration of ATLCAR.CD30 following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ refractory/relapsed HL and NHL.

To estimate the objective response rate as defined by the Lugano Classification78 for CAR.CD30 transduced ATL following lymphodepletion with bendamustine when administered in adult patients with CD30+ relapsed/refractory HL and NHL.

To estimate the objective response rate as defined by the Lugano Classification78 for CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine when administered in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.

To estimate duration of response after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine in adult patients with CD30+ relapsed/refractory HL and NHL

To estimate duration of response after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL

To further describe the adverse events associated with CAR.CD30 transduced ATL when administered in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.

To evaluate the safety of bendamustine alone or combined with fludarabine as lymphodepleting agents prior to infusion of CAR.CD30 transduced ATL in adult patients.

To evaluate the safety of bendamustine and fludarabine as lymphodepleting agents prior to infusion of CAR.CD30 transduced ATLs in pediatric patients.

To measure the survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine.

To measure the survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine and fludarabine.

To measure patient-reported symptom, physical function, and health-related quality of life at baseline and over time in adult patients treated with CAR.CD30 T cells.

Primary Endpoint (Phase Ib)

Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) and Cytokine Release Syndrome (CRS) toxicity will be graded according to the CRS Management Guidelines and CRS Toxicity Grading Scale

Primary Endpoint (Phase II)

PFS is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a result of any cause per the Lugano classification

Secondary Endpoints

Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to date of death and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion.

Progression free survival is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a result of any cause per the Lugano classification78 and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion.

The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) as determined by the Lugano classification78 and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion.

The duration of response will be defined as time from documentation of tumor response to disease progression and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion.

Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). S

Persistence of CAR.CD30 T cells in vivo will be determined by quantitative PCR and flow cytometry in peripheral blood samples and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion.

For adult patients: Patient reported symptoms will be measured using selected symptoms from the NCI PRO-CTCAE. Patient-reported physical function will be measured using the PROMIS Physical Function Score derived from the PROMIS Physical Function Short Form 20a v1.0. Patient-reported health-related quality of life will be measured using the PROMIS Global Health Score derived from the PROMIS Global Health Short Form v1.0-1.1.

OUTLINE

Cell Procurement

Up to 100 mL per collection (up to 3 collections) of peripheral blood will be obtained from patients for cell procurement. In patients with low (CD3 count as assayed by flow cytometry less than 200/μl) T-cell count in the peripheral blood, a leukopheresis may be performed to isolate sufficient T cells. The parameters for pheresis will be 2 blood volumes.

ATLCAR.CD30 Cells Administration

ATLCAR.CD30 cells will be administered as described below 1-14 days (preferably 1-2 days) after lymphodepletion with bendamustine and fludarabine. ATLCAR.CD30 cells will be given by a licensed provider (oncology nurse or physician) via intravenous injection over 1-10 minutes through either a peripheral or a central line. The expected volume will be 1-50cc. Patients with a partial response or stable disease at 6 weeks may receive a second infusion of ATLCAR.CD30 if cells are available. Note: Lymphodepletion with bendamustine and fludarabine will occur for three consecutive days and may be given prior to a second infusion of cells (if applicable).

Duration of Therapy

Therapy in Lineberger Comprehensive Cancer Center (LCCC) 1532 involves 1-2 infusions of ATLCAR.CD30 cells. Treatment with one infusion will be administered unless:

* Patient decides to withdraw from study treatment, OR
* General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.

Duration of Follow-up

Patients will be followed for up to 15 years for Replication Competent Retrovirus (RCR) evaluation or until death, whichever occurs first. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.

Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL

Phase Ib/II Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) for Relapsed/Refractory CD30+ Hodgkin's Lymphoma and CD30+ Non-Hodgkin's Lymphoma

Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE

PFS is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a results of any cause per the Lugano classification.

Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to the date of death and will be measured in subjects receiving a combination of bendamustine and fludarabine for lymphodepletion.

Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to date of death and will be measured in subjects receiving bendamustine alone.

Progression free survival is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a result of any cause per the Lugano classification and will be measured in subjects receiving bendamustine alone.

Progression free survival is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a result of any cause per the Lugano classification and will be measured in subjects receiving a combination of bendamustine and fludarabine for lymphodepletion.

The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) as determined by the Lugano classification and will be measured in subjects receiving bendamustine alone for lymphodepletion.

The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) as determined by the Lugano classification and will be measured in subjects receiving bendamustine and fludarabine for lymphodepletion.

Duration of response will be defined as time from documentation of tumor response to disease progression and will be measured in subjects receiving bendamustine alone for lymphodepletion.

Duration of response will be defined as time from documentation of tumor response to disease progression and will be measured in subjects receiving a combination of bendamustine and fludarabine for lymphodepletion.

Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0).

Persistence of CAR.CD30 T cells in vivo will be determined by quantitative PCR and flow cytometry in peripheral blood samples and will be measured in subjects receiving bendamustine alone for lymphodepletion.

Persistence of CAR.CD30 T cells in vivo will be determined by quantitative PCR and flow cytometry in peripheral blood samples and will be measured in subjects receiving bendamustine in combination with fludarabine for lymphodepletion

The NCI Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a patient-reported outcome measurement system developed to characterize the frequency, severity and interference of 78 symptomatic treatment toxicities. Each item is scored from 0 to four.

The PROMIS Global Health Short Form is a 10-item instrument representing multiple domains relating to overall health. Each item has a scale from 1 (poor) to 5 (excellent). Item 7, 8, and 10 are recoded. The global physical health score is generated by summing responses to Global03, Global06, Global07 rescored, Global08 rescored. The Global Mental Health score is generated by summing responses to Global02, Global04, Global05, Global10 Rescored.

The PROMIS Physical Function short form is a 20 item instrument that measures self-reported capability rather than actual performance of physical activities. This includes the functioning of one's upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back), as well as instrumental activities of daily living, such as running errands. Each item has five response options ranging in value from 1 (unable to do) to 5 (without any difficulty). To items are summed to find the overall raw score.

Antibodies, Monoclonal

Immunologic Factors

HeFi-1 Monoclonal Antibody

Background:

* Some cancers, such as Hodgkin's disease, anaplastic large cell lymphoma and others, have a protein on the surface of the cancer cell called CD30.
* HeFi-1 is an antibody that binds to the CD30 protein and sends signals to the cancer cells that can cause them to die.

Objectives:

* To determine the highest dose of HeFi-1 that can safely be given to patients with tumors that have the CD30 protein.
* To determine the response of the tumor to treatment with HeFi-1.

Eligibility:

* Patients 18 years of age and older with Hodgkin's disease, anaplastic large cell lymphoma, cutaneous T cell lymphoma and adult T cell leukemia or lymphoma who have signs of tumor growth or recurrence following standard treatment
* Patients' tumor cells must have the CD30 protein.

Design:

* Groups of three patients are treated with increasingly higher doses of HeFi-1 (ranging from 0.5 to 5 mg/kg) to determine the highest safe dose.
* HeFi-1 is infused through a vein on 4 days, followed by 2 days of rest over a 10-day period. Patients may receive up to 2 treatment courses if they show some response and do not have severe side effects.
* Blood samples are collected several times during the study to determine safety. A lymph node biopsy is done at the beginning of the study to test the effect of HeFi-1 on cancer cells in the test tube, and a bone marrow biopsy may be done at the end of treatment if the bone marrow was positive for tumor cells at the beginning of treatment.

BACKGROUND:

The scientific basis for this study is the observation that antibodies directed at the ligand-binding site of CD30 induce apoptosis in vitro and cure animals bearing CD30-positive tumors.

HeFi-1, a murine monoclonal antibody developed at the NCI, specifically binds human CD30, a member of the tumor necrosis receptor superfamily, at the ligand-binding site.

CD30 is expressed on activated T-cells, Reed-Sternberg cells, anaplastic large cell lymphoma, and some AIDS-related lymphoma cells.

Tumor cells from patients with anaplastic large cell lymphoma are sensitive to the effects of HeFi-1 but Hodgkin's disease cell lines show variable responsiveness due to the presence of mutations in I B kinase which result in constitutive activation of NF- B.

OBJECTIVE:

The primary objective of this study is to determine the toxicity and maximum tolerated dose of HeFi-1 in patients with CD30-positive malignancy.

This study will explore the pharmacokinetics, dose required to saturate CD30 binding sites in tumor aspirates, and the frequency and time course of onset of development of human anti-mouse antibody (HAMA).

These studies will allow us to monitor in a preliminary fashion the clinical tumor response, measured by reduction in tumor lesions and by following the tumor marker serum soluble interleukin 2 receptor.

ELIGIBILITY:

Patients with measurable or evaluable CD30-positive lymphoma who have become refractory to standard therapy, including Hodgkin's disease, systemic anaplastic large cell lymphoma, cutaneous T cell lymphoma and adult T cell leukemia/lymphoma are eligible for treatment.

DESIGN:

This is a phase I dose-escalation trial in which cohorts of three patients will be treated with HeFi-1 ranging from 0.5 to 5 mg/kg/dose (total dose of 2 to 20 mg/kg per treatment course).

Four doses will be given on an every three days schedule over a 10-day period for each cycle.

Two cycles of therapy will be administered provided the patient has had a partial or complete response and has not developed dose-limiting toxicity or HAMA.

Phase I Study of HeFi-1 to Treat Cancers With CD30 Protein

Phase I Study of HeFi-1 in Refractory CD30-Positive Malignancy

National Cancer Institute (NCI)

Antirheumatic Agents

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Rituximab

Vincristine

Brentuximab Vedotin

Dacarbazine

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Immunotoxins

Immunoconjugates

Intermediate Risk Patients (Stage IA bulk/E, IB, IIA bulk/E, IIB, IIIA): 4 cycles of chemotherapy

High Risk Patients (Stage IIIA bulk/ E, IIIB, IVA/B): 6 cycles of chemotherapy

Day 1 and 15 Dose: 1.2 mg/kg/dose. (Maximum dose is 120 mg)

Brentuximab vedotin

1 and 15 Dose: 1.5 mg/m2/dose (max: 2 mg/dose).

375 mg/m2 will be administered on days 1 and 15

Yanlong Duan

The goal of this clinical trial is to use modified Brentuximab Vedotin+doxorubicin+vinblastine+dacarbazine+Rituximab(BV-AVD-R) regimen in Chinese Classical Hodgkin's Lymphoma(HL) children. The main questions it aims to answer are:

* \[Overall Response Rate(ORR) :Complete Response(CR)+Partial Response(PR)\]
* \[progression-free survival (PFS), event-free survival (EFS) and overall survival (OS) at 6 months and 1 year.\] Participants will be given modified BV-AVD-R regimen according to rapid early responders (RER) or slow early responders (SER) after 2 cycles.

This study is a prospective study with period from October 2022 to December 2024, and planned to enroll 44 children with newly diagnosed intermediate- and high-risk classical HL. All patients will undergo Positron Emission Tomography(PET)/Computed Tomography(CT) at the time of initial diagnosis and after 2 cycles of modified BV+R+AVD regimen to determine early response. Rapid early responders (RER) deﬁned as CR after 2 cycles of therapy. Slow early responders (SER) defined as no CR (partial response (PR) or stable disease) after 2 cycles of therapy. Intermediate-risk patients were stage IA bulk/E, IB, IIA bulk/E, IIB, and IIIA. High-risk patients were stage IIB bulk/E, IIIA bulk/E, IIIB, and IVA/B.

The primary endpoints include ORR (CR+PR) and adverse events. The secondary endpoints include progression-free survival (PFS), event-free survival (EFS) and overall survival (OS) at 6 months and 1 year.

BV-AVD-R Treatment Children Hodgkin's Lymphoma

Efficacy and Safety of Modified BV-AVD-R Regimen in Chinese Children With Previously Untreated Intermediate- and High-risk Classical Hodgkin's Lymphoma: an Open Label, Non-randomized, Single-arm, Phase 2 Study From Single Center

Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)

disease evaluations will be performed by PET-CT at the end of randomized regimen

disease evaluations will be performed at at 6 months and 1 year after the end of treatment

Beijing Children's Hospital

Assocoate chief physician

Three dose levels of ATLCAR.CD30 cells will be evaluated. Using the modified continual reassessment method (CRM), initial cohort of size two will be enrolled at each dose level after that subjects are enrolled one at a time until a minimum of 12 patients is treated. Each patient will receive one injection according to the dosing schedules listed below. Investigators will start with the lowest cell dose (2X10\^7 cells/m\^2) given to patients in one of our previous trials employing CAR-T cells including the CD28 costimulatory endodomain, and investigators will escalate the cell dose to the highest cell dose (2X10\^8/m\^2) given in the same trial.

Note: Initially, only adults will be enrolled during the dose escalation phase of the study. Once a dose level has been tested in at least 2 adults without the occurrence of dose limiting toxicities (DLTs), children may then be enrolled on that dose level according to the CRM.

Three dose levels will be evaluated:

Group One, 2x10\^7 cells/m\^2 (maximum dose 5x10\^7 cells)

Group Two, 1x10\^8 cells/m\^2 (maximum dose 2.5x10\^8 cells)

Group Three, 2x10\^8 cells/m\^2 (maximum dose 5x10\^8 cells)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and CTCL	NCT03602157	Lymphoma Immune System D... Immunoprolifera... Lymphatic Disea... Lymphoprolifera... Neoplasms Cutaneous Lymph... Cutaneous Anapl... Mycosis Fungoid... Sezary Syndrome Lymphomatoid Pa... Cutaneous T Cel... Gray Zone Lymph...	ATLCAR.CD30.CCR... ALTCAR.CD30 cel... Bendamustine Fludarabine	18 Years -	UNC Lineberger Comprehensive Cancer Center
A Clinical Research of CD30-Targeted CAR-T in Lymphocyte Malignancies	NCT02958410	Leukemia Lymphoma	Anti-CD30-CAR-t...	14 Years - 75 Years	Southwest Hospital, China
Combination CAR-T Cell Therapy Targeting Hematological Malignancies	NCT03125577	B-cell Malignan...	4SCAR19 and 4SC... 4SCAR19 and 4SC... 4SCAR19 and 4SC... 4SCAR19 and 4SC... 4SCAR19 and 4SC... 4SCAR19 and 4SC...	6 Months - 75 Years	Shenzhen Geno-Immune Medical Institute
AFM13 in Relapsed/Refractory Cutaneous Lymphomas	NCT03192202	Lymphoma, T-Cel...	AFM13	18 Years -	Columbia University
Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL	NCT02690545	Lymphoma Lymphoma, Non-H... Immune System D... Immunoprolifera... Lymphatic Disea... Lymphoprolifera... Neoplasms Neoplasms by Hi...	ATLCAR.CD30 cel...	3 Years -	UNC Lineberger Comprehensive Cancer Center
Phase I Study of HeFi-1 to Treat Cancers With CD30 Protein	NCT00048880	Neoplasms	HeFi-1 Monoclon...	18 Years -	National Institutes of Health Clinical Center (CC)
BV-AVD-R Treatment Children Hodgkin's Lymphoma	NCT06201507	Hodgkin Lymphom...	Brentuximab ved... Rituximab Doxorubicin Vincristine Dacarbazine	- 18 Years	Beijing Children's Hospital
Administration of T Lymphocytes for Prevention of Relapse of Lymphomas	NCT02663297	Hodgkin Disease Lymphoma Lymphoma, Non-H... Immune System D... Immunoprolifera... Lymphatic Disea... Lymphoprolifera... Neoplasms Neoplasms by Hi...	ATLCAR.CD30 cel...	3 Years -	UNC Lineberger Comprehensive Cancer Center
Phase I Study of HeFi-1 to Treat Cancers With CD30 Protein	NCT00048880	Neoplasms	HeFi-1 Monoclon...	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for cd30

Every month we try and update this database with for cd30 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cd30

Every month we try and update this database with for cd30 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cd30 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.