A Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia

Study Overview
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Brief Summary
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Patients with relapsed or refractory leukemia often develop resistance to chemotherapy and some patients who relapse following CD19 directed therapy relapse with CD19 negative leukemia. For this reason, the investigators are attempting to use T-cells obtained directly from the patient, which can be genetically modified to express two chimeric antigen receptors (CARs). One is to recognize CD19 and the other is to recognize CD22, both of which are proteins expressed on the surface of the leukemic cell in patients with CD19+CD22+ leukemia. The CAR enables the T-cell to recognize and kill the leukemic cell through recognition of CD19 and CD22. This is a phase 1 study designed to determine the safety of the CAR+ T-cells and the feasibility of making enough to treat patients with CD19+CD22+ leukemia.

Official Title
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Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-05: A Phase 1 Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: Patient-derived CD19- and CD22 specific CAR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First 2 subjects: male and female subjects age ≥18 and < 27 years (as of 2/16/18 the first 2 subjects were enrolled and treated); subsequent subjects <31 years. Diagnosis of CD19+22+ leukemia Disease status: If post allogeneic HCT: Confirmed CD19+CD22+ leukemia recurrence defined as at least 0.01% disease following allogeneic HCT If relapse/refractory status with no prior history of allogeneic HCT, one of the following: Second or greater marrow relapse, with or without extramedullary disease First marrow relapse at end of first month or re-induction with marrow having at least 0.01 % blasts by morphology and/or MPF Primary refractory as defined as greater than 5% blasts by multi-parameter flow after at least 2 separate induction regimens. Subject has indication for HCT but has been deemed ineligible, inclusive of persistent MRD prior to HCT Asymptomatic from CNS involvement, if present, and in the opinion of the Principal Investigator with a reasonable expectation that disease burden can be controlled in the interval between enrollment and T-cell infusion. Subjects with significant neurologic deterioration will not be eligible for T-cell infusion until stabilized. Free from active GVHD and off immunosuppressive GVHD therapy for 4 weeks prior to enrollment Lansky or Karnofsky performance score of at least 50 Life expectancy of at least 8 weeks Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy At least 7 days post last chemotherapy administration (excluding intrathecal maintenance chemotherapy) At least 7 das post last systemic corticosteroids administration (unless physiologic replacement dosing) No prior genetically modified cell therapy that is still detectable or virotherapy Adequate organ function Adequate laboratory values Willing to participate in long-term follow-up for up to 15 years, if enrolled in the study and receive T cell infusion Patients of childbearing/fathering potential must agree to use highly effective contraception from the time of initial T cell infusion through 12 months following the last T cell infusion Exclusion Criteria: Presence of active clinically significant CNS dysfunction Pregnant or breast-feeding Unable to tolerate apheresis procedure Presence of active malignancy other than CD19+CD22+ leukemia Presence of active severe infection Presence of any concurrent medical condition that, in the opinion of the Principal Investigator, would prevent the patient from undergoing protocol-specified therapy

Ages Eligible for Study
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Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patient-derived CD19- and CD22 specific CAR v1<br>Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt | Biological: Patient-derived CD19- and CD22 specific CAR<br>* Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt<br>|
| Experimental: Patient-derived CD19- and CD22 specific CAR v2<br>Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt | Biological: Patient-derived CD19- and CD22 specific CAR<br>* Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The adverse events associated with one or multiple CAR T-cell product infusions will be assessed | Type, frequency, severity, and duration of adverse events will be summarized | 30 days | 
| The number of successfully and unsuccessfully manufactured and infused CAR T-cell products will be assessed | Proportion of products successfully manufactured and infused | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD19, CD22, CAR T-cell