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CD4CAR for CD4+ Leukemia and Lymphoma

ConditionsT-cell LymphomaT-cell Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age12+
SponsorHuda Salman

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must voluntarily sign and date informed consent forms that state his or her willingness to comply with all study procedures and availability for the duration of the study.

Age 12 years old or older

Subjects with any documented CD4+ T cell hematologic malignancies. Male and female subjects with CD4+ T-cell hematologic malignancies with either relapsed or refractory disease (including those patients who have undergone a prior transplant (if allogeneic, subjects are eligible if there are no remaining donor cells) and patients with an inadequate response after 4-6 cycles of standard chemotherapy) are eligible. Response criteria for each disease subset will be evaluated based on Standard of Care Guidelines.

Creatinine clearance of > 60 ml/min (or otherwise non clinically-significant, per study investigator)

Disqualifiers

Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential (see definition below) must have a negative serum or urine pregnancy test prior to initiation of conditioning chemotherapy, per research sites' clinical policy.

Uncontrolled active infection necessitating systemic therapy.

Active hepatitis B or hepatitis C infection. Active hepatitis C is defined as the hepatitis C antibody is positive while quantitative HCV RNA results exceed the lower detection limit.

Subjects with a history of hepatitis B but have received antiviral therapy and have nondetectable viral DNA for 6 months prior to enrollment are eligible

Trial design

Design model

Single group

Treatments tested in this trial

  • CD4CAR

    Biological/Vaccine

    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

Treatment groups

20 Participants
are divided into 1 treatment group
Group A: TreatmentExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

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.

Time frame
18-24 months

Secondary outcomes

1

Duration of in vivo survival of the CD4CAR.

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

Time frame
18-24 months
2

Rate of manufacturing failure

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.

Time frame
18-24 months
3

Clinical Response

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.

Time frame
18-24 months
4

Trafficking of CD4CAR at tumor sites and at sites with significant toxicity

Quantification of both of CD4CAR by research flow cytometry 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.

Time frame
18-24 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Huda Salman

Lead sponsor

Indiana University

Sponsor institution

iCell Gene Therapeutics

Collaborator

National Institutes of Health (NIH)

Collaborator

Source ClinicalTrials.gov
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