BCMA Chimeric Antigen Receptor Expressing T Cells Therapy for Relapsed/Refractory Multiple Myeloma

Sponsor

Hrain Biotechnology Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03943472

Collaborator

Shanghai Changzheng Hospital (Other)

Enrollment

Location

Arms

33.8

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this clinical trial is to study the feasibility and efficacy of anti-B-Cell Maturation Antigen (BCMA) expressing T cells in treating patients with multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Biological: Anti-BCMA CAR-T cells Drug: Fludarabine Drug: Cyclophosphamide Drug: Immune inhibitors	Early Phase 1

Detailed Description

Participants with BCMA-positive relapsed/refractory multiple myeloma can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, Electrocardiograph, CT/MRI/PET, and blood draws. Participants receive chemotherapy prior to the infusion of BCMA CAR+ T cells. After the infusion, participants will be followed for side effects and effect of BCMA CAR+ T cells. Study procedures may be performed while hospitalized.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

A Phase I Clinical Trial of T-Cells Targeting B-Cell Maturation Antigen for Subjects With Relapsed/Refractory Multiple Myeloma

Actual Study Start Date :

Jul 8, 2019

Anticipated Primary Completion Date :

Nov 1, 2021

Anticipated Study Completion Date :

May 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: anti-BCMA CAR-T Administration of anti-BCMA CAR-T cells to patients with multiple myeloma	Biological: Anti-BCMA CAR-T cells Retroviral vector-transduced autologous T cells to express anti-BCMA CAR Drug: Fludarabine 30mg/m2/d Drug: Cyclophosphamide 300mg/m2/d
Experimental: anti-BCMA CAR-T+ Immune inhibitors Administration of anti-BCMA CAR-T cells + Immune inhibitors to patients with multiple myeloma	Biological: Anti-BCMA CAR-T cells Retroviral vector-transduced autologous T cells to express anti-BCMA CAR Drug: Fludarabine 30mg/m2/d Drug: Cyclophosphamide 300mg/m2/d Drug: Immune inhibitors Immune inhibitors

Arm

Intervention/Treatment

Experimental: anti-BCMA CAR-T

Administration of anti-BCMA CAR-T cells to patients with multiple myeloma

Biological: Anti-BCMA CAR-T cells

Retroviral vector-transduced autologous T cells to express anti-BCMA CAR

Drug: Fludarabine

30mg/m2/d

Drug: Cyclophosphamide

300mg/m2/d

Experimental: anti-BCMA CAR-T+ Immune inhibitors

Administration of anti-BCMA CAR-T cells + Immune inhibitors to patients with multiple myeloma

Biological: Anti-BCMA CAR-T cells

Retroviral vector-transduced autologous T cells to express anti-BCMA CAR

Drug: Fludarabine

30mg/m2/d

Drug: Cyclophosphamide

300mg/m2/d

Drug: Immune inhibitors

Immune inhibitors

Outcome Measures

Primary Outcome Measures

Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 5.0 [6 months]
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 5.0

Secondary Outcome Measures

Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm [8 weeks]
Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm
Duration of CAR-positive T cells in circulation [6 months]
Duration of CAR-positive T cells in circulation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Expected survival > 12 weeks
Diagnosis of Multiple Myeloma by MWG criteria 20
Patients previously received at least 3 different prior treatment regimens for multiple myeloma, including alkylating agent, protein inhibitors, and immunomodulator, and have disease progression in the past 60 days
Important organs function enough to tolerate this therapy
At least 90 days after stem cell transplantation
Accessible to intravenous injection, and no white blood cell collection contraindications
Sexually active patients must be willing to utilize one of the more effective birth control methods for 30 days after the CTL infusion. Male partner should use a condom
Able to understand and sign the Informed Consent Document.

Exclusion Criteria:

Patients with symptoms of central nervous system
Patients with second malignancies in addition to multiple myeloma
Active hepatitis B or C, HIV infections
Any other active diseases could affect the enrollment of this trial
Suffering severe cardiovascular or respiratory disease
Poorly controlled hypertension
Long term use of immunosuppressive agents after organ transplantation, except currently receiving or recently received glucocorticoid treatment
A history of mental illness and poorly controlled
Screening showing target cell transduction efficacy is lower than 30%, or T cell proliferation is not enough for infusion (less than 5 fold)
Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
Women of child-bearing potential who are pregnant or breastfeeding during therapy, or have a planned pregnancy with 2 months after therapy
Women of child-bearing potential who are not willing to practice birth control from the time of enrollment on this study and for 2 months after receiving the preparative regimen. Women of child bearing potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
Active systemic infections or uncontrolled infection within 14 days prior enrollment
Subjects suffering disease affects the understanding of informed consent or complying with study protocol.