CD22-CAR T Cells in Children and Young Adults With B Cell Malignancies

Phase 1

Active, not recruiting

• Conditions: Acute Lymphoblastic Leukemia, Pediatric; B Cell Lymphoma; Lymphoma
• Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Autologous CD22 CAR T

• Registration Number: NCT04088864
• Lead Sponsor: Stanford University

Brief Summary

The primary purpose of this study is to test whether CD22-CAR T cells can be successfully made from immune cells collected from pediatric and young adult subjects with relapsed/refractory B-cell malignancies (leukemia and lymphoma). Another purpose of this study is to test the safety and cancer killing ability of a cell therapy against a new cancer target (CD22).

Detailed Description

PRIMARY OBJECTIVE:

* Determine the feasibility of manufacturing CD22 CAR T cells for administration to children and young adults with relapsed/refractory (R/R) CD22 expressing B-cell ALL or lymphoma using the Miltenyi CliniMACS Prodigy system.

* Determine the safety of an established dose of CD22-CAR T cells in children and young adults with R/R CD22 expressing B-cell malignancies.

SECONDARY OBJECTIVE:

- Assess the clinical activity of CD22-CAR T cells in children and young adults with R/R CD22 expressing B-cell malignancies, including overall survival (OS) and progression free survival (PFS).

Study Timeline

• Study First Submitted: 2019-09-11
• Study First Submitted QC: 2019-09-11
• Study First Posted: 2019-09-13
• Study Start: 2020-01-10
• Primary Completion: 2023-10-31
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-09
• Last Update Posted: 2024-02-12
• Study Completion: 2036-09-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
R/R B-ALL	Autologous CD22 CAR T	Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide followed by infusion of CD22 CAR T cells on Day0. Lymphodepletion: * Fludarabine 25 mg/m2 per day IV for days 4, 3, -2 * Cyclophosphamide 900 mg/m2 per day IV on day -2 Autologous CD22 CAR T cells will be administered intravenously at Dose level 1 (1 x 10\^6 transduced T cells/kg (± 20%)).
Lymphoma	Autologous CD22 CAR T	Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide followed by infusion of CD22 CAR T cells on Day0. Lymphodepletion: * Fludarabine 25 mg/m2 per day IV for days 4, 3, -2 * Cyclophosphamide 900 mg/m2 per day IV on day -2 Autologous CD22 CAR T cells will be administered intravenously at Dose level 1 (1 x 10\^6 transduced T cells/kg (± 20%)).
R/R B-ALL	Cyclophosphamide	Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide followed by infusion of CD22 CAR T cells on Day0. Lymphodepletion: * Fludarabine 25 mg/m2 per day IV for days 4, 3, -2 * Cyclophosphamide 900 mg/m2 per day IV on day -2 Autologous CD22 CAR T cells will be administered intravenously at Dose level 1 (1 x 10\^6 transduced T cells/kg (± 20%)).
R/R B-ALL	Fludarabine	Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide followed by infusion of CD22 CAR T cells on Day0. Lymphodepletion: * Fludarabine 25 mg/m2 per day IV for days 4, 3, -2 * Cyclophosphamide 900 mg/m2 per day IV on day -2 Autologous CD22 CAR T cells will be administered intravenously at Dose level 1 (1 x 10\^6 transduced T cells/kg (± 20%)).
Lymphoma	Cyclophosphamide	Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide followed by infusion of CD22 CAR T cells on Day0. Lymphodepletion: * Fludarabine 25 mg/m2 per day IV for days 4, 3, -2 * Cyclophosphamide 900 mg/m2 per day IV on day -2 Autologous CD22 CAR T cells will be administered intravenously at Dose level 1 (1 x 10\^6 transduced T cells/kg (± 20%)).
Lymphoma	Fludarabine	Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide followed by infusion of CD22 CAR T cells on Day0. Lymphodepletion: * Fludarabine 25 mg/m2 per day IV for days 4, 3, -2 * Cyclophosphamide 900 mg/m2 per day IV on day -2 Autologous CD22 CAR T cells will be administered intravenously at Dose level 1 (1 x 10\^6 transduced T cells/kg (± 20%)).

Primary Outcome Measures

Name	Time	Method
Rate of successful manufacture of CD22 CAR T cells	7-11 days after apheresis	The percentage of apheresis samples (fresh or frozen) that are successfully processed and expanded to manufacture CD22 CAR T cells that satisfy the target dose level and meet release specifications will be determined for each disease group (ALL or lymphoma).
Safe dose of CD22-CAR T cells in subjects with R/R B-cell malignancies	28 days after infusion	Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD22 CAR T cells, as recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at target dose of 1 x 10\^6 transduced T cells/kg (± 20%).

Secondary Outcome Measures

Name	Time	Method
Clinical activity of CD22-CAR T cells in adults with R/R lymphoma	3 months after infusion of CD22-CAR T cells	Clinical activity will be assessed by Lugano response criteria for lymphoma. Results will be reported as best response (i.e. complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PR)) at Month 3 for adult lymphoma/DLBCL subjects treated at Maximum tolerated dose (MTD) /recommended phase 2 dose (RP2D).
Clinical activity of CD22-CAR T cells in children and young adults with R/R CD22-expressing B-cell ALL and R/R lymphoma	28 days after infusion of CD22-CAR T cells	Clinical activity will be assessed by modified International Working Group response criteria for acute lymphoblastic leukemia (ALL). Results will be reported as best response (i.e. complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PR)) at Day 28 for adult subjects with ALL treated at the target dose.

Trial Locations

Locations (1)

Stanford Medical Center; 🇺🇸 Stanford, California, United States