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

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.

Study Overview

• Status: Unknown
• Conditions: Lymphoma; Leukemia; Multiple Myeloma
• Intervention / Treatment: Biological: Anti-BCMA-CAR-transduced T cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Recruiting
      • Southwest Hospital of Third Millitary Medical University
      • Contact: Zhi Yang, PhD; Phone Number: 008613206140093; Email: yz2003can@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Biological: 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.; Other Names: BCMA-targeted CAR-T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events That Are Related to Treatment	Determine the toxicity profile of the BCMA targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Reaction Rate of Treatment	3 years
In vivo existence of Anti-BCMA CAR-T cells	3 years

Collaborators and Investigators

• Sponsor: Southwest Hospital, China
• Investigators: Principal Investigator: Cheng Qian, MD, PhD, Biotherapy Center of Southwest Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Anticipated): October 1, 2019
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimate): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): June 25, 2019
• Last Update Submitted That Met QC Criteria: June 23, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: CAR-T; BCMA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Multiple Myeloma
• Other Study ID Numbers: TMMU-BTC-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED