Phase I Trial Study of Anti-BCMA (B-cell Maturation Antigen) or/and Anti-CD19 Chimeric Antigen Receptor T Cells (CART Cell) Treatment for the Patient of Relapsed Multiple Myeloma
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Multiple Myeloma in Relapse
- Sponsor
- Shenzhen Second People's Hospital
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- No Dose-limiting toxicity
- Last Updated
- 7 years ago
Overview
Brief Summary
This phase I trial studies the side effects and best dose of BCMA CART cells in treating patients with BCMA positive multiple myeloma that have not respond to chemotherapy and autologous Hematopoietic Stem Cell Transplantation (Auto-HSCT). B-cell maturation antigen (BCMA), a cell surface protein expressed on mutiple maloma cells, has emerged as a very selective antigen to be targeted in novel immunotherpy for MM. Targeting postulated CD19 positive myeloma stem cells with anti-CD19 CAR-T cells is a novel approach to MM therapy.
Detailed Description
This is multi-center, phase I trial that studies the side effects and best dose of BCMA CART cells in treating patients with BCMA positive multiple myeloma that have not respond to chemotherapy and autologous Hematopoietic Stem Cell Transplantation (Auto-HSCT). B-cell maturation antigen (BCMA), a cell surface protein expressed on mutiple maloma cells , has emerged as a very selective antigen to be targeted in novel immunotherpy for MM. Targeting postulated CD19+ myeloma stem cells with anti-CD19 CAR-T cells is a novel approach to MM therapy.
Investigators
Wei-Hong Chen, MD
professor, Chief physician, principal investigator
Shenzhen Second People's Hospital
Eligibility Criteria
Inclusion Criteria
- •Have the capacity to give informed consent
- •Have measurable disease by International Myeloma Working Group (IMWG) criteria based on one or more of the following findings:
- •Serum M-protein \>= 1 g/dL
- •Urine M-protein \>= 200 mg/24 hour
- •Involved serum free light chain (sFLC) level \>= 10 mg/dL with abnormal κ/λ ratio
- •Measurable biopsy-proven plasmacytomas (\>= 1 lesion that has a single diameter \>= 2 cm)
- •Bone marrow plasma cells \>= 30%
- •Have a diagnosis of BCMA+ multiple myeloma (MM) (\>= 5% BCMA+ by flow cytometry on CD138 co-expressing plasma cells obtained within 45 days of study enrollment); the MM diagnosis must be confirmed by internal pathology review of a fresh biopsy specimen at the Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA)
- •Have relapsed or treatment refractory disease with \>= 10% CD138+ malignant plasma cells (IHC) on bone marrow (BM) core biopsy, either:
- •Following autologous stem cell transplant (ASCT)
Exclusion Criteria
- •Active hepatitis B, hepatitis C at the time of screening
- •Patients who are (human immunodeficiency virus \[HIV\]) seropositive
- •Subjects with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis
- •\> 1 hospital admission for infection in prior 3 months
- •Presence of acute or chronic graft-versus-host disease (GVHD) unless limited to skin involvement and managed with topical steroid therapy alone
- •History of any one of the following cardiovascular conditions within the past 6 months: class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
- •History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, active central nervous system MM involvement and/or carcinomatous meningitis; subjects with previously treated central nervous systems involvement may participate, provided they are free of disease in the CNS (documented by flow cytometry performed on the cerebrospinal fluid (CSF) within one week of enrollment) and have no evidence of new sites of CNS activity
- •Pregnant or nursing women; NOTE: Women of reproductive potential must have a negative serum pregnancy test performed within 48 hours of starting conditioning chemotherapy
- •Use of any of the following:
- •Therapeutic doses of corticosteroids (defined as \> 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis; physiologic replacement, topical, and inhaled steroids are permitted
Outcomes
Primary Outcomes
No Dose-limiting toxicity
Time Frame: up to 5 mouths after T cell infusion
No Dose-limiting toxicity