Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

All Drugs and Chemicals

Ibalizumab

Redirected autologous T cells transduced with the anti-CD4 lentiviral vector (referred to as "CD4CAR" cells)

CD4CAR cells transduced with a lentiviral vector to express the single-chain variable fragment (scFv) nucleotide sequence of the anti-CD4 molecule derived from humanized monoclonal ibalizumab and the intracellular domains of CD28 and 4-1BB co-activators fused to the CD3ζ T-cell activation signaling domain administered by IV infusions as a single dose

CD4CAR

Tara Haney, RN

Huda Salman, MD, PhD

This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-redirected chimeric antigen receptor engineered T-cells (CD4CAR) in patients with relapsed or refractory AML. the study will evaluate safety in this patient population and also the presence of efficacy signal described by elimination of residual disease to qualify patients for stem cell transplant.

The study will be performed as a dose-escalation protocol. The investigators expect to recruit 20 subjects at Indiana University with an expected dropout rate of 25% primarily due to rapid progression or death and screen and or manufacturing failure. Taking this into account, the investigators expect to treat 15 patients. The study will utilize autologous CD4CAR T-cells that are engineered to express a chimeric antigen receptor (CAR) targeting CD4 that is linked to the cluster of differentiation 28 (CD28), 4-1BB, cluster of differentiation 3-zeta (CD3ζ) signaling chains (third generation CAR). about 70% of AML with monocytic differentiation and 37% of all the rest express CD4 on their blasts.

At entry, disease status will be staged. Qualifying subjects will be leukapheresed to obtain large numbers of peripheral blood mononuclear cells (PBMC) for the manufacturing. Next, participants will receive conditioning chemotherapy. If tumor burden is sufficiently reduced (screening step), participants will receive CD4CAR cells by infusion on Day 0 of treatment.

If the disease progresses during the manufacturing period participants may be excluded from the study or an attempt to bridge for disease control will be offered. Minimal chemotherapy to keep the disease under control in the meanwhile is allowed if deemed necessary by investigators.

A single dose of CD4CAR transduced T cells will consist of the cell number for the dose level to be infused.

Post-infusion monitoring of CD4CAR T-cells: Subjects will have blood drawn for cytokine levels, CD4CAR Transgene Copy Number (PCR) and flow cytometry in order to evaluate the presence of CD4CAR cells on days 0, 1, 3, 5, 7, 14, and 28 following infusion (or as clinically needed). Cytokines levels will be evaluated per schedule above in addition to and as needed every 8 +/- 2 hours as feasible if/when Cytokine Release Syndrome, CRS, occurs and until resolution. Active monitoring of fungal and viral infections during treatment while utilizing standard prophylaxis recommended for HIV-positive patients with T-cell aplasia and those undergoing allogeneic stem cell transplant. Investigators plan to collect data about clinicoradiologic measurements of residual tumor burden starting on day 7 and weekly afterward until Day 28 and then monthly for 6 months. This will be followed by quarterly clinical evaluations for the next two (2) years with a medical history, physical examination, and comprehensive blood testing. After these short- and intermediate-term evaluations are performed, these patients will enter a rollover study to assess for disease-free survival (DFS), relapse, and the development of other health problems or malignancies where follow-up will be up to twice a year by phone and a questionnaire for an additional thirteen (13) years. The treating physician will decide to proceed with allogeneic or autologous transplant when needed.

Dose of CD4CAR description: the main objective of this study is to establish a recommended dose and/or schedule of CD4CAR. The guiding principle for dose escalation in phase I is to avoid unnecessary exposure of patients to sub-therapeutic doses (i.e., to treat as many patients as possible within the therapeutic dose range) while preserving safety and maintaining rapid accrual. Investigators will use the rule-based traditional Phase I "3+3" design for the evaluation of safety. Based on lab experience in mice the starting dose (dose level 1) for the first cohort of three patients in phase I portion of the study will be 8x10\^5 cells. The dose escalation or de-escalation will follow a modified Fibonacci sequence as below.

If more than one patient out of the first cohort of three patients in dose level 1 experience dose limiting toxicity (DLT), the trial will be placed on hold. If zero or one out of three patients in the first cohort of dose level 1 experience DLT, three more patients will be enrolled at dose level 1; the dose escalation continues until at least two patients among a cohort of six patients experience DLT (i.e., ≥33% of patients with a DLT at this dose level)

If one of the first three patients in dose level 1 experiences a DLT, three more patients will be treated at dose level 1.

If none of the three patients or only one of the 6 patients in the dose level 1 experiences a DLT, the dose escalation continues to the dose level 2 If one of the first three patients in dose level 2 experience a DLT, three more patients will be treated at dose level 2 If none of the three patients or only one of the 6 patients in the dose level2 experiences a DLT, the dose escalation continues to the dose level 3 If one of the first three patients in dose level 3 experiences a DLT, three more patients will be treated at dose level 3 If none of the three patients or only one of the 6 patients in the dose level 3 experiences a DLT, dose level 3 will be declared the maximum tolerated dose (MTD) and will be used as the recommended phase II dose (RP2D) for the phase II portion of the study.

In summary, the dose escalation continues until at least two patients among a cohort of six patients experience DLT (i.e., ≥33% of patients with a DLT at that dose level). The recommended dose for phase II trials is defined as one dose level below this toxic dose level. Since some grade 3 and possibly 4 toxicities are highly likely to be reversible, grade 3 infectious, hematological and vascular toxicities will not be considered DLTs mandating dose reduction. Also allergic or infusion-related reactions ≤ grade 3 will not be counted as DLTs. There will be no intra-patient dose escalation or reduction.

To allow for full spectrum toxicity duration evaluation and reporting, no patients within the same or a different cohort will be initiated on lymphodepleting chemotherapy sooner than 28 days from the initiation date of the preceding patient.

Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory Acute Myeloid Leukemia (AML ) as a Bridge to Allogeneic Stem Cell Transplant

Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory AML as a Bridge to Allogeneic Stem Cell Transplant

In this traditional phase 1 dose escalation, cohorts of three subjects will be treated on a dose level that will be incremented to next dose level if no dose limiting toxicities (DLT) were reported or expanded if a DLT is documented.

The persistence of the CAR through day 28 and possibly longer if detected by D28. This will be performed by flow to assess for the CD3+/Fab2+ cell population The phenotype of the CAR will be determined by flow as well, to look for Tcm phenotype

1. Examine the efficacy of CD4CAR on changing the frequency of T regs subpopulation after CD4CAR infusion as compared to their frequency prior to treatment.
2. Determine the impact of the change in T regs and MDSCs abundance on objective response to CD4CAR.

Examine the efficacy of CD4CAR on changing the frequency of MDSCs subpopulation

Participants' blood will be tested by flow cytometry to determine the ability of CD4CAR to target Monocytic Leukemia Stem Cells (mLSCs).

Participants blood will be examined for cytokine level changes according to time points as described in the protocol.

Tha treatment is intended to reduce the disease burden enough to qualify patients for stem cell transplant through either elimination of residual disease or minimizing that to being acceptable to transplant consideration. to assess this, Change on percentage of leukemia blasts or their total disappearance will be used to quantify patients responses to partial versus complete responders consecutively.

Huda Salman

Director, Hematologic Malignancies Service and Director, CAR T Cellular Therapy Program

Immune System Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Leukemia, T-Cell

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Leukemia, T-cell, Chronic

Dose escalation phase: CD4 CAR T cells transduced with a lentiviral vector to express CD4 chimeric receptor domain on T cells with an escalation approach, 2e6 to 5e6 CAR-T cells/kg

CD4 CAR T cells administered to patients, will be either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy.

CD4 CAR T cells

Kevin Pinz, MS

Yupo Ma, MD/PhD

Hongyu Zhang, MD/PhD

Fang Liu, MD/PhD

This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of CD4 CAR T cells in patients with relapsed and/or refractory T cell lymphoma.

CD4-specific CAR is a chimeric antigen receptor immunotherapy treatment designed to treat lymphoma/leukemia expressing CD4 antigen. CD4+ T cell lymphomas are a subset of leukemias and lymphomas that are positive for the surface protein CD4. The purpose of this study is to evaluate the efficacy and safety of CD4 CAR T cells.

CD4-specific CAR T Cells (CD4 CAR T Cells) for Relapsed/Refractory T Cell Malignancies

Determine the toxicity profile of CD4 CAR T cell therapy

Incidence of treatment-emergent adverse events

Disease Free Survival (DFS) (IMWG criteria)

Progression-Free Survival (IMWG criteria)

iCAR Bio Therapeutics Ltd.

Peking University Shenzhen Hospital

iCell Gene Therapeutics

Hematologic Neoplasms

Leukemia, Lymphoid

Huda Salman, MD

Amer Beitinjaneh, MD

Anakrystine Vallin

This study is designed as a single arm open label Phase I, 3x3, multicenter study of CD4-directed chimeric antigen receptor engineered T-cells (CD4CAR) in patients with relapsed or refractory T-cell leukemia and lymphoma. Specifically, the study will evaluate the safety and feasibility of CD4CAR T-cells. Funding Source - FDA OOPD

The study will be performed as a dose-escalation protocol. Due to the relatively low incidence and prevalence of cluster of differentiation 4-positive (CD4+) hematological malignancies and the associated aggressive nature of these diseases and the sequel of treatment failure, the investigators expect to recruit 20 subjects at Stony Brook, Indiana University, and other identified sites with an expected dropout rate of 25% primarily due to rapid progression or death and screen and or manufacturing failure. Taking this into account, the investigators expect to treat 15 patients. The study will utilize autologous CD4CAR T-cells that are engineered to express a chimeric antigen receptor (CAR) targeting CD4 that is linked to the cluster of differentiation 28 (CD28), 4-1BB, cluster of differentiation 3-zeta (CD3ζ) signaling chains (third generation CAR).

At entry, disease status will be staged and investigators will determine if the subject has adequate T cell number for apheresis and for manufacturing CD4CAR cells. Qualifying subjects will be leukapheresed to obtain large numbers of peripheral blood mononuclear cells (PBMC) for the manufacturing. Next, participants will receive conditioning chemotherapy. If tumor burden is sufficiently reduced (screening step), participants will receive CD4CAR cells by infusion on Day 0 of treatment.

For cell harvest, 12-15-liter apheresis procedure will be performed at the apheresis center with the intention to harvest at least 50x10\^9-nucleated cells to manufacture CD4CAR T-cells. A portion of the pheresed cells will also be cryopreserved for FDA look-back requirements and for further research. The T-cells will be purified from the PBMC, transduced with CD4CAR lentiviral vector, expanded in vitro, and then frozen for administration. Each dose will be stored in either one or two bags. The route of administration is by IV infusion and the duration of infusion will be approximately 20 minutes. Each bag will contain an aliquot (30-50 mL) of liquid suitable for freezing, and containing the following infusible grade reagents (% v/v): 62.5cc Plasmalyte-A 5% dextrose; 7.5cc Pure dimethylsulfoxide (DMSO), 20cc of 25% Human Serum Albumin, and 10cc Dextran 40. The cell product is expected to be ready for release approximately 3-4 weeks after apheresis.

If the disease progresses during the manufacturing period participants may be excluded from the study. Minimal chemotherapy to keep the disease under control in the meanwhile is allowed if deemed necessary by investigators.

A single dose of CD4CAR transduced T cells will consist of the cell number for the dose level to be infused.

Post-infusion monitoring of CD4CAR T-cells: Subjects will have blood drawn for cytokine levels, CD4CAR Transgene Copy Number (PCR) and flow cytometry in order to evaluate the presence of CD4CAR cells on days 0, 1, 3, 5, 7, 14, 28, and 42 following infusion (or as clinically needed). Cytokines levels will be evaluated per schedule above in addition to and as needed every 8 +/- 2 hours as feasible if/when CRS occurs and until resolution. Active monitoring of fungal and viral infections during treatment while utilizing standard prophylaxis recommended for HIV-positive patients with T-cell aplasia and those undergoing allogeneic stem cell transplant. Investigators plan to collect data about clinicoradiologic measurements of residual tumor burden starting on day 6 and weekly afterward until day 42 and then monthly for 6 months. This will be followed by quarterly clinical evaluations for the next two (2) years with a medical history, physical examination, and comprehensive blood testing. After these short- and intermediate-term evaluations are performed, these patients will enter a rollover study to assess for disease-free survival (DFS), relapse, and the development of other health problems or malignancies where follow-up will be up tp twice a year by phone and a questionnaire for an additional thirteen (13) years. The treating physician will decide to proceed with allogeneic or autologous transplant when needed.

Dose of CD4CAR description: the main objective of this study is to establish a recommended dose and/or schedule of CD4CAR. The guiding principle for dose escalation in phase I is to avoid unnecessary exposure of patients to sub-therapeutic doses (i.e., to treat as many patients as possible within the therapeutic dose range) while preserving safety and maintaining rapid accrual. Investigators will use the rule-based traditional Phase I "3+3" design for the evaluation of safety. Based on lab experience in mice the starting dose (dose level 1) for the first cohort of three patients in phase I portion of the study will be 8x10\^5 cells. The dose escalation or de-escalation will follow a modified Fibonacci sequence as below.

If more than one patient out of the first cohort of three patients in dose level 1 experience dose limiting toxicity (DLT), the trial will be placed on hold. If zero or one out of three patients in the first cohort of dose level 1 experience DLT, three more patients will be enrolled at dose level 1; the dose escalation continues until at least two patients among a cohort of six patients experience DLT (i.e., ≥33% of patients with a DLT at this dose level)

* If one of the first three patients in dose level 1 experiences a DLT, three more patients will be treated at dose level 1.
* If none of the three patients or only one of the 6 patients in the dose level 1 experiences a DLT, the dose escalation continues to the dose level 2
* If one of the first three patients in dose level 2 experience a DLT, three more patients will be treated at dose level 2
* If none of the three patients or only one of the 6 patients in the dose level2 experiences a DLT, the dose escalation continues to the dose level 3
* If one of the first three patients in dose level 3 experiences a DLT, three more patients will be treated at dose level 3
* If none of the three patients or only one of the 6 patients in the dose level 3 experiences a DLT, dose level 3 will be declared the maximum tolerated dose (MTD) and will be used as the recommended phase II dose (RP2D) for the phase II portion of the study.

In summary, the dose escalation continues until at least two patients among a cohort of six patients experience DLT (i.e., ≥33% of patients with a DLT at that dose level). The recommended dose for phase II trials is defined as one dose level below this toxic dose level. Since some grade 3 and possibly 4 toxicities are highly likely to be reversible, grade 3 infectious, hematological and vascular toxicities will not be considered DLTs mandating dose reduction. Also allergic or infusion-related reactions ≤ grade 3 will not be counted as DLTs. There will be no intra-patient dose escalation or reduction.

To allow for full spectrum toxicity duration evaluation and reporting, no patients within the same or a different cohort will be initiated on lymphodepleting chemotherapy sooner than 42 days from the initiation date of the preceding patient.

CD4CAR for CD4+ Leukemia and Lymphoma

A Phase I, Multicenter Study of CD4- Directed Chimeric Antigen Receptor Engineered T-cells (CD4CAR) in Patients With Relapsed or Refractory CD4+ Hematological Malignancies

To assess the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD4 lentiviral vector (referred to as "CD4CAR" cells) according to CTCAE grading. The feasibility of treating those adverse events and their duration till resolution will also be described.

Persistence of CD4CAR will be monitored by measuring the CD4CAR transgene copy number at variable time points.

The number of failed manufacturing attempts of CD4 CAR, per subject and overall, in this patient population. Manufacturing failure is defined as failure to manufacture the adequate CD4CAR cell dose for the particular cohort the patient is enrolled on. Three manufacturing attempts per patient are allowed.

Clinical response to T-cell infusion will be evaluated by comparing disease before and after infusion identified by:

* standard imaging (PET CT or PET MRI) for lymphoma patients
* bone marrow biopsy for leukemia patients
* peripheral blood cells morphology, flow cytometry panel, immunohistochemistry, and other blood molecular markers for both lymphoma and leukemia.

Quantification of both of CD4CAR by flowcytometry and transgene copy number by polymerase chain reaction (PCR) will be measured at tumor sites in bone marrow and lymph nodes at variable time points if applicable. Same tests will be done on biopsies of organs that shows significant toxicity if need be.

The absolute and relative number of subjects who develop immune reactions against the treatment over a period of 2 years. Human anti-mouse antibody (HAMA) ELISA tests will be carried out in the blood of participants at multiple times after initial treatment.

Serum cytokine levels will be evaluated on Day 2, 4, 7, 11, 14, 21, 28 in addition to planned monitoring during CRS every 8 hours and until resolution. These cytokines include interleukin-6 (IL-6), interferon-γ, tumor necrosis factor, IL-2, IL-2-receptor-a, IL-8, and IL-10

Participants' blood will be tested by flow cytometry to determine the relative abundance of cellular subsets that may result from CD4CAR T cells upon their proliferation. These subsets include Tcm, Tem, and Tregs.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory Acute Myeloid Leukemia (AML ) as a Bridge to Allogeneic Stem Cell Transplant	NCT06197672	Acute Myeloid L...	CD4CAR	18 Years -	Indiana University
CD4-specific CAR T Cells (CD4 CAR T Cells) for Relapsed/Refractory T Cell Malignancies	NCT04162340	T Cell Lymphoma... Refractory T-Ce...	CD4 CAR T cells	18 Years -	iCell Gene Therapeutics
CD4CAR for CD4+ Leukemia and Lymphoma	NCT03829540	T-cell Lymphoma T-cell Leukemia	CD4CAR	12 Years -	Indiana University
Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory Acute Myeloid Leukemia (AML ) as a Bridge to Allogeneic Stem Cell Transplant	NCT06197672	Acute Myeloid L...	CD4CAR	18 Years -	Indiana University
CD4CAR for CD4+ Leukemia and Lymphoma	NCT03829540	T-cell Lymphoma T-cell Leukemia	CD4CAR	12 Years -	Indiana University
CD4-specific CAR T Cells (CD4 CAR T Cells) for Relapsed/Refractory T Cell Malignancies	NCT04162340	T Cell Lymphoma... Refractory T-Ce...	CD4 CAR T cells	18 Years -	iCell Gene Therapeutics
CD4CAR for CD4+ Leukemia and Lymphoma	NCT03829540	T-cell Lymphoma T-cell Leukemia	CD4CAR	12 Years -	Indiana University

Spots Global Cancer Trial Database for cd4car

Every month we try and update this database with for cd4car 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 cd4car

Every month we try and update this database with for cd4car 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 cd4car 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.