Human BCMA Targeted T Cells Injection Therapy for BCMA-positive Relapsed/Refractory Multiple Myeloma

NCT ID: NCT04003168

Last Updated: 2021-03-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-01
• Study Completion Date: 2024-07-31

Brief Summary

To evaluate the safety and efficacy of Human BCMA Targeted T Cells Injection for the treatment of BCMA-positive relapsed/refractory multiple myeloma. Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of BCMA CAR+ T cells.

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.

Conditions

Multiple Myeloma

Study Design

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

Study Groups

Human BCMA targeted T Cells Injection

A single infusion of anti-BCMA CAR transduced T cells administered intravenously at a target dose of 3 to 9 x 10\^6 CAR T +cells/kg. The classic "3+3" dose escalation will be applied.

Group Type: EXPERIMENTAL

Human BCMA targeted T Cells Injection

Intervention Type: DRUG

Autologous genetically modified anti-BCMA CAR transduced T cells

Interventions

Human BCMA targeted T Cells Injection

Autologous genetically modified anti-BCMA CAR transduced T cells

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Subjects volunteer to participate in clinical research, understand and know the research and sign informed consent document, willing to complete all the trial procedures;

2. 18 to 70 Years Old, Male and female;

3. Expected survival > 12 weeks;

4. Previously diagnosed as multiple myeloma by IMWG updated criteria (2014);

5. Patients with positive pathological test results or flow cytometry proving that BCMA expression of malignant plasma cells in bone marrow or plasma cell tumors ≥30%;

6. One of the following indicators is satisfied:

1. Serum M protein IgG ≥ 10 g/L, or IgA > 10 mg/L, or IgD > 5 mg/L;

2. Urine M protein ≥ 200 mg/24h;

3. Serum free light chain ≥ 100 mg/L;

7. Patients with relapsed/refractory multiple myeloma. Relapsed is defined as:

Patients have disease progression after at least three-line treatment regimens. Patients previously received at least 3 different mechanisms treatment regimens for multiple myeloma, including protease inhibitors and immunomodulators, and have disease progression within 60 days of the latest treatment ; Refractory is defined as: Patients who achieved remission in the piror therapies, have disease progression within 60 days, or after the latest therapy.

8. Those who relapse 90 days after stem cell transplantation

9. ECOG score 0-1;

10. Liver, kidney and cardiopulmonary functions meet the following requirements:

1. Creatinine clearance (estimated by Cockcroft Gault formula) ≥ 40 mL/min;

2. Left ventricular ejection fraction >50%;

3. Baseline peripheral oxygen saturation >95%;

4. Total bilirubin ≤ 2×ULN; ALT and AST ≤2.5 × ULN;

11. The venous access required for collection can be established, and no leukocyte collection contraindications.

Exclusion Criteria

1. Accompanied by other uncontrolled malignancies;

2. Subjects with positive HBsAg or HBcAb and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; syphilis primary screening antibody positive;

3. Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), severe arrhythmia, liver, kidney or metabolic disease with poor drug control;

4. Patients who are accounted to be not appropriate for this trail by investigator;

5. Pregnant or lactating, or planning to have a pregnancy during or within 1 year after treatment;

6. Received CAR-T treatment or other gene therapies before enrollment;

7. Those who failed to sign informed consent form or comply with the research procedures; Unwilling or unable to comply with research requirements;

8. Have had severe immediate hypersensitivity reactions to any drugs used in this research;

9. The presence or suspicion of fungi, bacteria, viruses or other infections that are uncontrollable or requiring intravenous treatment;

10. In the past two years, the terminal organ was damaged due to autoimmune diseases (such as crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the systemic use of immunosuppressive or other systemic disease control drugs was required;

11. Have a history of central nervous system (CNS) disease, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain damage, dementia, Parkinson's disease, psychosis.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Changzheng Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: collaborator

The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine

OTHER

Sponsor Role: collaborator

Hrain Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine

Zhengzhou, Henan, China

Site Status: RECRUITING

Shanghai Changzheng Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hongliang Fang, doctor

Role: CONTACT

fanghongliang@dashengbio.com

021-58552006

Facility Contacts

Zhi Cheng, M.D.

Role: primary

clinicaltrials.chengzhi@outlook.com

+(86)-139-3852-6995

Weijun Fu, Professor

Role: primary

fuweijun2010@hotmail.com

021-81885423

Kang Yu, Professor

Role: primary

yukang62@126.com

0577-55579486

References

Wang H, Tsao ST, Gu M, Fu C, He F, Li X, Zhang M, Li N, Hu HM. A simple and effective method to purify and activate T cells for successful generation of chimeric antigen receptor T (CAR-T) cells from patients with high monocyte count. J Transl Med. 2022 Dec 19;20(1):608. doi: 10.1186/s12967-022-03833-6.

Reference Type: DERIVED

PMID: 36536403 (View on PubMed)

Other Identifiers

HRAIN01-MM01

Identifier Type: -

Identifier Source: org_study_id