Co-administration of CART22-65s and huCART19 for B-ALL

Stephan Grupp MD PhD

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: B Lineage Lymphoblastic Lymphoma; B-cell Acute Lymphoblastic Leukemia

Treatments: Biological: Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s); Biological: Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)

Study type: Interventional

Funder types: Other

Identifiers

NCT05674175

22CT015 (Other Identifier)

22-020640

Details and patient eligibility

About

This study will evaluate the safety and efficacy of administering two CAR T cell products, huCART19 and CART22-65s, in children with advanced B cell Acute Lymphoblastic Leukemia (B-ALL).

Full description

CD19-targeted CAR T cell therapy has transformed the treatment landscape for children and young adults with chemo-refractory or relapsed B cell Acute Lymphoblastic Leukemia (B-ALL). Despite remarkable initial response rates, approximately 50% of pediatric patients experience a subsequent disease relapse. The prognosis for these patients is dismal with a median survival of less than one year from the time of post-CART19 relapse. The primary mechanisms contributing to CART19 failure include CD19-antigen escape and loss of CAR T cell surveillance due to short CART persistence. This study aims to counter each driver of relapse by co-administering two next-generation CAR T cell products: an anti-CD22 CART (CART22-65s), designed to overcome CD19-antigen escape; and a humanized anti-CD19 CART (huCART19), designed to overcome immune-mediated rejection of murine CART19.

Enrollment: 93 estimated patients

Sex: All

Ages: Under 29 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Signed informed consent form

2. Patients with documented CD19+ and/or CD22+ ALL/LLy:

   1. Cohort A: Patients with relapsed or refractory ALL/LLy:
   2. Cohort B: Patients with poor response to prior B cell directed engineered cell therapy

3. Patients with prior or current history of Central Nervous System 3 disease will be eligible if Central Nervous System disease is responsive to therapy

4. Documentation of CD19 and/or CD22 tumor expression in bone marrow, peripheral blood, Cerebrospinal fluid, or tumor tissue by flow cytometry at the time of last detectable disease. If the patient has experienced a relapse after CD19-directed and/or CD22-directed therapy, flow cytometry should be evaluated after this therapy to demonstrate CD19 and/or CD22 expression.

5. Age 0-29 years

6. Adequate organ function

7. Adequate performance status defined as Lanksy or Karnofsky performance score ≥50.

8. Subjects of reproductive potential must agree to use acceptable birth control methods.

Exclusion criteria

1. Active hepatitis B or active hepatitis C
2. HIV infection
3. Active acute or chronic Graft Vs. Host Disease requiring systemic therapy
4. Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
5. Central nervous system disease that is progressive on therapy, or with Central nervous system parenchymal lesions that might increase the risk of central nervous system toxicity.
6. Pregnant or nursing (lactating) women
7. Uncontrolled active infection

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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93 participants in 2 patient groups

Dose Finding Arm

Experimental group

Description:

Phase 1 will evaluate the safety of co-administration of CART22-65s with huCART19 in patients who experienced a disease relapse after prior CAR T cell therapy. There is no planned dose escalation but a dose-deescalation will be made based on the incidence of Dose Limiting Toxicities

Treatment:

Biological: Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)

Biological: Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s)

Expansion Arm

Experimental group

Description:

If at least one dose level of phase 1 is determined to be safe, the phase 2 dose expansion phase of the trial will be opened to enrollment. Subjects will receive the highest dose of CART 22-65s and huCART19 cells that were determined to be safe. 2 cohorts are planned: Cohort A (relapsed/refractory, CAR T cell naïve) \& Cohort B (prior treatment with a prior CAR T cell product).

Treatment:

Biological: Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)

Biological: Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s)