Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by Tandem CAR T Cells Targeting CD19 and CD20

Phase 1

Completed

• Conditions: B-cell Adult Acute Lymphoblastic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Hematopoietic/Lymphoid Cancer; Recurrent Grade 1 Follicular Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 3 Follicular Lymphoma
• Interventions: Biological: anti-CD19/20-CAR vector-transduced T cells

• Registration Number: NCT03097770
• Lead Sponsor: Chinese PLA General Hospital

Brief Summary

RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.

PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in treating patients with B-cell leukemia or lymphoma that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to chemotherapy.

Detailed Description

PRIMARY OBJECTIVES:

To assess the efficacy of TanCAR19/20 T cells in relapsed or refractory NHL, defined as overall response rate (ORR).

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of TanCAR19/20 T cells. II. To evaluate time to response (TTR), duration of overall response (DOR), progression free survival (PFS) and overall survival (OS).

III. To determine in vivo expansion and persistence of TanCAR19/20 T cells.

OUTLINE: Patients are assigned to 1 group according to order of enrollment. Patients receive anti-CD19/20-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on day1 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 3 years.

Study Timeline

• Study First Submitted: 2017-03-26
• Study First Submitted QC: 2017-03-26
• Study First Posted: 2017-03-31
• Study Start: 2017-04-01
• Primary Completion: 2019-05-10
• Status Verified: 2019-12
• Study Completion: 2020-01-31
• Last Update Submitted: 2020-08-31
• Last Update Posted: 2020-09-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Not provided

Exclusion Criteria

Patients eligible for this study must not meet any of the following criteria:

1. Patients with definite involvement of gastrointestinal tract. Endoscopy should be performed to conform gastrointestinal involvement for patients suspected. However, patients with central nervous system (CNS) involvement were cautiously enrolled in this clinical study.
2. CD19 CAR T cell treatment failure or recurrence, detection of a clear HAMA effect, or negative tumour puncture detection of CD19 and CD20.
3. Pregnant or lactating women.
4. Uncontrolled active bacterial or viral infection. (active hepatitis B or hepatitis C infection, HIV infection) or treponema pallidum infection.
5. Class III/IV cardiovascular disability according to the New York Heart Association Classification and a cardiac ejection fraction ≥50%.
6. History of allogeneic stem cell transplantation.
7. Any autoimmune disease or primary immunodeficiency.
8. Requirement for urgent therapy due to tumour mass effects such as respiratory obstruction or blood vessel compression.
9. Current or expected need for systemic corticosteroid therapy.
10. Any organ failure.
11. The patients with the second tumour requiring for therapy or intervention.
12. Subjects considered unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation according to the investigator's judgement.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
anti-CD19/20 CAR T cells	anti-CD19/20-CAR vector-transduced T cells	Patients receive anti-CD19/20-CAR retroviral vector-transduced autologous or donor-derived T cells on day 1 in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Occurrence of study related adverse events	Until week 24	defined as \>= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment

Secondary Outcome Measures

Name	Time	Method
Anti-tumor responses to tanCART19/20 cell infusions	up to 96 weeks

Trial Locations

Locations (1)

Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China