Autologous CD22 CAR T Cells in Adults w/ Recurrent or Refractory B Cell Malignancies

Phase 1

Active, not recruiting

• Conditions: B-ALL; DLBCL; Follicular Lymphoma Grade 3B; B-cell Non Hodgkin Lymphoma
• Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: CD22 CAR

• Registration Number: NCT04088890
• 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 adults with relapsed/refractory B-cell malignancies (leukemia and lymphoma).

Detailed Description

Primary Objective:

* Determine the feasibility of manufacturing CD22 CAR T cells using the Miltenyi CliniMACS Prodigy® system for administration to adults with relapsed/refractory CD22 expressing B-cell ALL or relapsed/refractory aggressive B-cell non hodgkins lymphoma (NHL).

* Establish the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of CD22 CAR T cells in adults with relapsed/refractory aggressive B-cell NHL.

* Determine the safety of an established dose of CD22-CAR T cells in adults with relapsed/refractory CD22 expressing B-cell ALL and the safety of the MTD/RP2D of CD22-CAR T cells in adults with relapsed/refractory aggressive B-cell NHL.

Secondary Objective:

- Assess the clinical activity of CD22-CAR T cells in adults with R/R CD22 expressing B-cell ALL and R/R aggressive B-cell NHL, including overall survival (OS) and progressive free survival (PFS).

Study Timeline

• Study First Submitted: 2019-09-11
• Study First Submitted QC: 2019-09-11
• Study Start: 2019-09-12
• Study First Posted: 2019-09-13
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-24
• Last Update Posted: 2024-07-25
• Primary Completion: 2024-12-30
• Study Completion: 2037-12-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
R/R ALL	CD22 CAR	Relapsed/refractory ALL Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22 CAR T cells will be administered intravenously at Dose1: 3 x 10\^5cells/kg (± 20%) 10
R/R aggressive B-cell NHL	CD22 CAR	Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) to determine MTD/RP2D. Dose1: 1 x 10\^6 cells/kg (± 20%) Dose2: 3 x 10\^6 cells/kg (± 20%) Dose3: 1 x 10\^7 cells/kg (± 20%)
R/R ALL	Fludarabine	Relapsed/refractory ALL Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22 CAR T cells will be administered intravenously at Dose1: 3 x 10\^5cells/kg (± 20%) 10
R/R ALL	Cyclophosphamide	Relapsed/refractory ALL Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22 CAR T cells will be administered intravenously at Dose1: 3 x 10\^5cells/kg (± 20%) 10
R/R aggressive B-cell NHL	Fludarabine	Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) to determine MTD/RP2D. Dose1: 1 x 10\^6 cells/kg (± 20%) Dose2: 3 x 10\^6 cells/kg (± 20%) Dose3: 1 x 10\^7 cells/kg (± 20%)
R/R aggressive B-cell NHL	Cyclophosphamide	Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) to determine MTD/RP2D. Dose1: 1 x 10\^6 cells/kg (± 20%) Dose2: 3 x 10\^6 cells/kg (± 20%) Dose3: 1 x 10\^7 cells/kg (± 20%)

Primary Outcome Measures

Name	Time	Method
Rate of successful manufacture of CD22 CAR T cells	7-11 days from start of manufacturing	The percentage of apheresis samples (fresh or frozen) that are successfully processed and expanded to manufacture CD22 CAR T cells will be determined for each dose cohort.
MTD/RP2D of CD22-CAR T cells in subjects with aggressive B-cell NHL	28 days after infusion of CD22 CAR T cells	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 each dose level tested in subjects with aggressive B-cell NHL
Safety evaluation of CD22-CAR T cells in subjects with ALL	2 years after infusion of CD22-CAR T cells	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 each dose level tested in subjects with ALL

Secondary Outcome Measures

Name	Time	Method
Clinical activity of CD22-CAR T cells in adults with relapsed/refractory aggressive B-cell NHL at MTD/RP2D	3 months after infusion of CD22-CAR T cells	Clinical activity will be assessed by Lugano response criteria for lymphoma (see Appendix 13.3.2). 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 aggressive B-cell NHL subjects treated at MTD/RP2D.
Clinical activity of CD22-CAR T cells in adults with relapsed/refractory CD22-expressing B-cell ALL at target dose	28 months after infusion of CD22-CAR T cells	Clinical activity will be assessed by modified International Working Group response criteria for acute lymphoblastic leukemia. 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