Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma

NCT ID: NCT02685670

Last Updated: 2017-03-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2019-12-31

Brief Summary

This is a single-arm open-label phase I/II study to determine the relative superiority of αCD19-TCRζ-CD28 and αCD19-TCRζ-CD137 CAR-T Cells in safety, efficacy and engraftment potential in patients with CD19+ B-lineage leukemia and lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. In this trial, all subjects will be competitively infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number to test a hypothesis that CD137-costimulation can promote the persistence and engraftment of CAR-T cells and this superiority can lead to improved progression-free survival.

Detailed Description

Primary objectives

1. To determine the safety and feasibility of adoptive transfer of T cells modified to express CD19-specific chimeric antigen receptor (CD19CAR) for treatment of leukemia and lymphoma

Secondary objectives

1. To measure the efficacy of anti-tumor responses after CD19CAR T cell infusion

2. To determine if CD19CAR T cells engineered with 4-1BB signaling domain is superior to that with CD28 signaling domain for their homing and persistence after CD19CAR T cell infusion

Conditions

Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mixed CD19CAR transfer

All subjects will be infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number

Group Type: EXPERIMENTAL

anti-CD19 CAR-T

Intervention Type: BIOLOGICAL

Ex vivo-expanded autologous T cells modified to express CD19 CAR

Fludarabine

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Interventions

anti-CD19 CAR-T

Ex vivo-expanded autologous T cells modified to express CD19 CAR

Intervention Type: BIOLOGICAL

Fludarabine

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 5 Years to 70 Years, Male and female;

2. Expected survival > 12 weeks;

3. Performance score 0-2;

4. Histologically confirmed as CD19-positive lymphoma/leukemia and who meet one of the following conditions;

• Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
• Disease recurrence after stem cell transplantation;
• Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy

5. Creatinine < 2.5 mg/dl;

6. ALT/AST < 3x normal;

7. Bilirubin < 2.0 mg/dl;

8. Adequate venous access for apheresis, and no other contraindications for leukapheresis;

9. Take contraceptive measures before recruit to this trial;

10. Written voluntary informed consent is given.

Exclusion Criteria

1. Patients with symptoms of central nervous system

2. Accompanied by other malignant tumor

3. Active hepatitis B or C, HIV infection

4. Any other diseases could affect the outcome of this trial

5. Suffering severe cardiovascular or respiratory disease

6. Poorly controlled hypertension

7. A history of mental illness and poorly controlled

8. Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration

9. Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment

10. Reaching a steady dose if receiving anticoagulant therapy before assignment

11. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion

12. Pregnant or lactating women

13. Subject suffering disease affects the understanding of informed consent or comply with study protocol.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xinqiao Hospital of Chongqing

OTHER

Sponsor Role: collaborator

Xuzhou Medical University

OTHER

Sponsor Role: collaborator

The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine

OTHER

Sponsor Role: lead

Responsible Party

Chengzhi

Director of Department of Hematology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhi Cheng, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine

Locations

Henan Province of TCM

Zhengzhou, Henan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhi Cheng, M.D.

Role: CONTACT

clinicaltrials.chengzhi@outlook.com

+(86)-139-3852-6995

Facility Contacts

Zhi Cheng, M.D.

Role: primary

Other Identifiers

DHHUTCM20160106

Identifier Type: -

Identifier Source: org_study_id