A Clinical Research of BCMA-Targeted CAR-T in B Cell Malignancies

NCT ID: NCT02954445

Last Updated: 2019-06-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2020-10-31

Brief Summary

The overall purpose of this study is to explore the therapeutic effect of BCMA-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of B-cell derived malignancies.

Detailed Description

B-cell maturation antigen(BCMA) is preferentially expressed in mature B lymphocytes as well as in B-cell derived leukemia, lymphomas, and multiple myeloma. Despite of the fact that CD19-targeted CAR-T can re-induce remissions for many patients with relapsed and refractory B cell malignancies, a part of those patients will relapse with CD19-negative malignancies. To explore a rescue for those with CD19-negative B cell malignancies, this trial is designed and conducted to test the safety and effect of BCMA-targeted CAR-T.

Conditions

Leukemia; Lymphoma; Multiple Myeloma

Study Design

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

Study Groups

B Cell Malignancies

The trial will be conducted in a manner of simon two-stage design with Anti-BCMA-CAR-transduced T cells, beginning in the first stage with the aim of over 30% reaction rate among 15 patients with B cell malignancies. Only when the expected reaction rate is achieved the 30 patients left can be recruited.

Group Type: EXPERIMENTAL

Anti-BCMA-CAR-transduced T cells

Intervention Type: BIOLOGICAL

The first 3 enrolled patients will receive autologous-derived BCMA-targeted CAR-T cells on day 1, 2 and 3 with respective 10%, 30% and 60% of the total expected dosage after receiving lymphodepleting chemotherapy. If the 3 patients don't display severe toxicity, the next patients enrolled will get infused in 2 days with respective 40% and 60% total dosage.

Interventions

Anti-BCMA-CAR-transduced T cells

The first 3 enrolled patients will receive autologous-derived BCMA-targeted CAR-T cells on day 1, 2 and 3 with respective 10%, 30% and 60% of the total expected dosage after receiving lymphodepleting chemotherapy. If the 3 patients don't display severe toxicity, the next patients enrolled will get infused in 2 days with respective 40% and 60% total dosage.

Intervention Type: BIOLOGICAL

Other Intervention Names

BCMA-targeted CAR-T cells

Eligibility Criteria

Inclusion Criteria

1. BCMA-expressing B cell malignancy must be assured and must be relapsed or refractory disease. According to current traditional therapies, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time.

2. Patients enrolled must have an evaluated score above 60 with KPS.

3. BCMA expression of the malignant cells must be detected by immunohistochemistry or by flow cytometry. In general immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples.

4. Gender is not limited, age from 14 years to 75 years.

5. Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.

6. Patients are expected to survive for more than 3 months by their physicians at the time of enrollment.

7. Adequate absolute CD3 count estimated need to be assured for obtaining target cell dose based on dosage cohorts.

8. Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:

CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs; CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm CNS3 with marrow disease who has failed salvage systemic and intensive IT chemotherapy (and therefore not eligible for radiation)

9. Ability to give informed consent.

10. Cardiac function: Left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO.

11. Renal function: Creatinine level of peripheral blood is required no greater than 133umol/L.

12. Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.

13. Patients with history of allogeneic stem cell transplantation are eligible if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.

14. Patients volunteer to participate in the research.

Exclusion Criteria

1. Evident signs suggesting that patients are potentially allergic to cytokines.

2. Frequent infection history and recent infection is uncontrolled.

3. Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome

4. Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.

5. Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications.

6. Pregnancy and nursing females.

7. HIV infection.

8. Active hepatitis B or active hepatitis C.

9. Participation in a prior investigational study within 4 weeks prior to enrollment or longer if required by local regulation. Participation in non-therapeutic research studies is allowed.

10. Class III/IV cardiovascular disability according to the New York Heart Association Classification.

11. Patients with a known history or prior diagnosis of other serious immunologic, malignant or inflammatory disease.

12. Other situations we think not eligible for participation in the research.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Southwest Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Shiqi Li

Principal Investigator of Biotherapy Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cheng Qian, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Biotherapy Center of Southwest Hospital

Locations

Southwest Hospital of Third Millitary Medical University

Chongqing, Chongqing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Cheng Qian, MD, PhD

Role: CONTACT

cqian3184@163.com

0086-023-68765461

Shiqi Li, MD

Role: CONTACT

yz2003can@126.com

0086-13206140093

Facility Contacts

Cheng Qian, PhD

Role: primary

cqian3184@163.com

008615086883400

Zhi Yang, PhD

Role: backup

yz2003can@126.com

008613206140093

Other Identifiers

TMMU-BTC-009

Identifier Type: -

Identifier Source: org_study_id