Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Fludarabine

Fludarabine phosphate

Bendamustine Hydrochloride

Subjects will be enrolled on 1 of 3 dose levels as determined by a 3+3 design. Up to 25 evaluable subjects may then be enrolled in the phase II portion of the study. Subjects may have cells procured to manufacture the ATLCAR.CD30.CCR4 cells if they meet eligibility for procurement. During the time period necessary to manufacture the ATLCAR.CD30.CCR4 cells, Subjects will be allowed to receive standard-of-care bridging therapy at the discretion of their local oncologist. Prior to cell infusion, subjects will undergo additional eligibility evaluations, and then if eligible, will undergo lymphodepletion followed by cell infusion 2-14 days later. Subjects will then be followed for 15 years as is required for studies involving gene transfer experiments

Subjects will receive a lymphodepletion regimen of bendamustine 70 mg/m2 IV and fludarabine 30 mg/m2 each as a daily infusion for 3 consecutive days prior to the ATLCAR.CD30.CCR4 cell infusion.

Chemotherapy

ATLCAR.CD30.CCR4 cells infusion for the eligible subjects after depletion chemotherapy.

Cell infusion

Catherine Cheng

Natalie Grover, MD

Despite the progress in the therapy, Hodgkin's Lymphoma (HL) remains fatal for more than 15% of patients. Even in patients who are cured, the morbidity of therapy is substantial and long-lasting. New therapeutic agents are required therefore not only to further reduce mortality but also to alleviate morbidity.

The majority of HL express the CD30 antigens. CD30 expression is routinely used for the diagnosis of HL. Preclinical observations support CD30 as a viable target of CAR-T therapy. This phase Ib/II study was conducted based on these observations.

The purpose of this study is to determine the tolerability of ATLCAR.CD30.CCR4 cells in subjects with Hodgkin's Lymphoma and identify a recommended dose for further.

This is a single-center, open-label phase Ib/II trial that uses a 3+3 design to identify a recommended phase 2 dose (RP2D) of ATLCAR.CD30.CCR4 cells in Hodgkin's Lymphoma. The phase II portion is designed to determine the PFS of ATLCAR.CD30.CCR4 in Hodgkin's Lymphoma.

Subjects will be enrolled on 1 of 3 dose levels as determined by a 3+3 design. Up to 25 evaluable subjects may then be enrolled in the phase II portion of the study. Subjects may have cells procured to manufacture the ATLCAR.CD30.CCR4 cells if they meet eligibility for procurement. During the time period necessary to manufacture the ATLCAR.CD30.CCR4 cells, Subjects will be allowed to receive standard-of-care bridging therapy at the discretion of their local oncologist. Prior to cell infusion, subjects will undergo additional eligibility evaluations, and then if eligible, will undergo lymphodepletion followed by cell infusion 2-14 days later. Subjects will then be followed for 15 years as is required for studies involving gene transfer experiments.

ATLCAR.CD30.CCR4 for CD30+ HL ATLCAR.CD30.CCR4 Cells

The Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) and CCR4 for Relapsed/Refractory CD30+ Hodgkin s Lymphoma

Toxicity will be graded as the Number of participants with adverse events (AE)s

AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dose Limiting Toxicities (DLTs) is defined as at least possibly related to CAR.B7-H3T cell product administration.

CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild: Fever ≥38\^ o C, No hypotension, No hypoxia, Grade 2 - Moderate: Fever ≥38\^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe: Fever ≥ 38\^ o C, Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (\>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening: Fever ≥38\^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death

Neurotoxicity will be graded according to the Immune effector cell-associated neurotoxicity syndrome (ICANS) criteria.

Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).

PFS will be defined as the time from the first day of lymphodepletion chemotherapy to cell infusion to progression by Lugano Criteria or death. Complete: Complete metabolic response on Positron emission tomography (PET) or the largest transverse diameter (LDi) of target nodes/masses ≤ 1.5 cm and no extra lymphatic disease on Computerized Tomography (CT). Partial: reduced uptake compared with baseline and residual mass(es) on PET and ≥50% decrease in the sum of the products of diameters (SPD) of nodes and extranodal sites on CT. No Response or Stable Disease: No metabolic response on PET or \< 50% decrease from baseline in SPD, measurable nodes and extranodal sites; no criteria for the progressive disease are met on CT. Progressive Disease: Score 4 or 5 with an increase in the intensity of uptake from baseline and/or new focus on PET, LDi\>1.5 cm or by ≥ 50% from nadir.

An event will be considered a Dose-limiting toxicity per NCI CTCAE version 5.0, the CRS Grading, and ICANS grading criteria.

* Grade 3-5 allergic reactions related to the CAR-T cell infusion.
* A treatment-emergent Grade 3 CRS that does not improve to Grade 0-1 by 72 hours or Grade 4 CRS
* Grade ≥3 ICANS that are unresponsive to the standard of care interventions and do not decrease to Grade ≤1 within 7 days or grade 4 ICANS of any duration that has evidence of cerebral edema and/or generalized convulsive status epilepticus.
* Any treatment-emergent Grade 4 non-hematologic AE that does not resolve to Grade 2 within 7 days.
* Any Grade 5 events are not due to the underlying malignancy.

OS is defined as the time from the first day of lymphodepletion to date of death for any cause. Subjects who have not had an event will be censored at the date of last assessment documenting the subject was alive.

DOR is defined as the time from partial response (PR) or better to progressive disease (PD) per Lugano Criteria. Complete Response: Complete metabolic response on Positron emission tomography (PET) or Target nodes/nodal masses must be ≤ 1.5 cm in the largest transverse diameter (LDi) or no extra lymphatic of disease on Computerized Tomography (CT). Partial Response: Score of 4 or 5† with reduced uptake of any size on PET and ≥50% decrease in the sum of the products of diameters (SPD) of nodes and extranodal sites on CT. No Response or Stable Disease: No metabolic response on PET or \< 50% decrease from baseline in SPD of nodes and extranodal sites; no criteria for the progressive disease are met on CT. Progressive Disease: Score 4 or 5 with an increase in the intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma.

UNC Lineberger Comprehensive Cancer Center

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Brentuximab Vedotin

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

Brentuximab vedotin at a fixed dose of 1.8 mg/kg will be administered by intravenous infusion on day 1 of every 21-day cycle. MLN8237 at a dose of 60 mg will be orally administered daily in 2 divided doses (30 mg qAM, 30 mg qPM) from days 1 to 7 of each 21-day cycle. MLN8237 dose will be escalated in 20-mg increments to the maximum dose of 100 mg (Level 2) or de-escalated in a 20-mg decrement to the minimum dose of 40 mg (Level -1).

Antibody-drug conjugate composed of the anti-CD30 chimeric immunoglobulin G1 monoclonal antibody cAC10 and the antimicrotubule drug monomethyl auristatin E connected by a protease-cleavable linker.

Alsertib

Swami Padmanabhan Iyer, MD

This is an open label phase I trial designed to evaluate the maximum tolerated dose, dose-limiting toxicities, pharmacokinetics, and activity of the combination of alsertib (MLN8237) and brentuximab vedotin in patients with relapsed/refractory CD30-positive lymphomas and solid malignancies. Cohorts of 3-6 patients will receive escalating or de-escalating doses of MLN8237 based on a 3 + 3 design.

This is an investigator-initiated, open label phase I trial designed to evaluate the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and activity of brentuximab vedotin in combination with MLN8237 in patients with relapsed/refractory CD30-positive lymphomas and solid malignancies.

Brentuximab vedotin at a fixed dose of 1.8 mg/kg will be administered on Day 1 every three weeks as a 30-minute outpatient intravenous infusion. MLN8237 will be orally administered in two divided doses from Days 1-7. The starting dose (level 0) of MLN8237 will be 60 mg daily given in two divided doses (30 mg qAM, 30 mg qPM).The dose of MLN8237 will be escalated in 20-mg increments up to 100 mg daily and de-escalated in 20-mg decrements to 40 mg daily. The fixed dose of brentuximab vedotin on Day 1 and daily dose of MLN8237 on Day 1-7 will constitute one treatment cycle. If no DLTs are observed in the last study cohort, the cohort will be expanded to include a total of 12 patients. If a de-escalation dose is required because 2 or more patients experience DLTs, the next lower cohort will be studied. If 2 or more patients do not experience DLTs, this dose will be declared the MTD. This cohort will be expanded to include 12 patients in order to study the biological endpoints and clinical benefit of the combination. If at any point during the expansion cohort phase of the trial 33% or more of the patients treated at the MTD/maximum administered dose experience a DLT, accrual of additional patients at this does level will cease and the next lowest dose may be explored.

Alsertib (MLN8237) and Brentuximab Vedotin for Relapsed/Refractory CD30-Positive Lymphomas and Solid Malignancies

A Phase I Study of the Combination of Alsertib (MLN8237) and Brentuximab Vedotin in Relapsed/Refractory CD30-Positive Lymphomas and Solid Malignancies

Data and materials on human subjects will be shared with other eligible investigators through appropriate means in accordance with the NIH policy on Sharing Research Data (NIH Guide, February 26, 2003). Data will be also shared with the funding agency and regulatory agencies as required. Data will be shared with other investigators within the limits of HIPAA and other patient confidentiality requirements. This will generally require removal of all patient identifiers for all source documents and the use of arbitrarily assigned one-way identifiers. In some cases, requestors will be asked to sign a formal data sharing agreement that will provide for a commitment to use data only for research purposes and not to identify individuals, keep the data secure, and destroy or return data after analyses are complete. Prior approval will be obtained from collaborating investigators, research sponsors, and/or other stake-holders before sharing if proprietary information or products are involved.

Measure H3K activity in peripheral blood mononuclear cells and tumor tissue following treatment with the combination of alsertib (MLN8237) and brentuximab vedotin.

Explore the correlation between CD30 detection method (aptamer-mediated flow cytometric detection vs. immunohistochemical detection) and clinical response to the combination of alsertib (MLN8237) and brentuximab vedotin.

Determine the MTD of the alsertib (MLN8237) and brentuximab vedotin combination in patients with relapsed/refractory CD30-positive lymphomas and solid malignancies.

Describe the DLTs and other toxicities associated with the alsertib (MLN8237) and brentuximab vedotin combination as assessed by CTCAE v4.0.

Determine the RP2D of the alsertib (MLN8237) and brentuximab vedotin combination.

Document the antitumor activity of the alsertib (MLN8237) and brentuximab vedotin combination as assessed by modified IWG criteria and RECIST 1.1.

Determine the area under the plasma concentration versus time curve of alsertib (MLN8237) and brentuximab vedotin.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
ATLCAR.CD30.CCR4 for CD30+ HL ATLCAR.CD30.CCR4 Cells	NCT06090864	Hodgkin Lymphom... Relapse Refractory	Chemotherapy Cell infusion	18 Years -	UNC Lineberger Comprehensive Cancer Center
Alsertib (MLN8237) and Brentuximab Vedotin for Relapsed/Refractory CD30-Positive Lymphomas and Solid Malignancies	NCT02780011	CD30-positive L... CD30-positive S...	Brentuximab Ved... Alsertib	18 Years -	The Methodist Hospital Research Institute

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.