CD4CAR for CD4+ Leukemia and Lymphoma
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|ClinicalTrials.gov Identifier: NCT03829540|
Recruitment Status : Active, not recruiting
First Posted : February 4, 2019
Last Update Posted : September 21, 2022
|Condition or disease||Intervention/treatment||Phase|
|T-cell Lymphoma T-cell Leukemia||Biological: CD4CAR||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I, Multicenter Study of CD4- Directed Chimeric Antigen Receptor Engineered T-cells (CD4CAR) in Patients With Relapsed or Refractory CD4+ Hematological Malignancies|
|Actual Study Start Date :||June 18, 2019|
|Estimated Primary Completion Date :||December 2025|
|Estimated Study Completion Date :||December 2037|
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 (total dose of up to ~4x106 T Cells/KG)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 18-24 months ]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.
- Duration of in vivo survival of the CD4CAR. [ Time Frame: 18-24 months ]Persistence of CD4CAR will be monitored by measuring the CD4CAR transgene copy number at variable time points.
- Rate of manufacturing failure [ Time Frame: 18-24 months ]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 [ Time Frame: 18-24 months ]
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.
- trafficking of CD4CAR at tumor sites and at sites with significant toxicity [ Time Frame: 18-24 months ]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.
- Number of participants with immune reactions against CD4CAR [ Time Frame: 18-24 months ]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 cytokines levels [ Time Frame: 18-24 months ]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
- determine CD4CAR cell subsets during proliferation [ Time Frame: 18-24 months ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03829540
|United States, Indiana|
|Indiana University Melvin and Bren Simon Comprehensive Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|Study Chair:||Huda Salman, MD||Indiana University|