Multiple Myeloma
Conditions
Brief summary
This trial aims to evaluate the safety and efficacy of BCMA-UCART in treating patients with relapsed or refractory multiple myeloma.
Detailed description
BCMA(B-Cell maturation antigen) is a tumor antigen of multiple myeloma. Using a genetic engineering strategy to assemble an anti-BCMA CAR(chimeric antigen receptor) in T cells will help these CART cells to recognize and kill BCMA-expressing MM tumor cells. BCMA-UCART is a kind of allogeneic CART, originating from T cells of health donors. This open-label, dose-escalation study aims to evaluate the safety and anti-tumor efficacy of BCMA-UCART in treating relapsed or refractory multiple myeloma.
Interventions
BIOLOGICALBCMA-UCART
A conditioning therapy with cyclophosphamide and fludarabine will be conducted for subjects before CART therapy.
Sponsors
Shanghai Tongji Hospital, Tongji University School of Medicine
Second Xiangya Hospital of Central South University
Bioray Laboratories
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
0.5-1\*10\ 6/KgBW, 1-2\*10\ 6/KgBW,2-3\*10\ 6/KgBW
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Have the capacity to give informed consent; * Confirmed diagnosis of active MM as defined by NCCN and IMWG criteria; * Have a diagnosis of BCMA+ multiple myeloma (MM), (≥ 5% BCMA+ in CD138+ plasma cells by flow cytometry obtained within 45 days of study enrollment); * Refractory and relapsed MM patients after \> 2 cycles of induction therapy,or,have relapsed or treatment refractory disease following autologous stem cell transplant (ASCT); * ECOG score=0-2. * Subjects according with any of the following options: * Age≥50; * Failure with separation of T cells during autologous CART processing; or, * Failure with expansion of autologous CART; or, * The proportion of T cells in PBMC \<10%; or, * Won't benefit from autologous CART therapy because of disease progress.
Exclusion criteria
* Pregnant or nursing women; Women of reproductive potential must have a negative serum pregnancy test performed within 48 hours of starting conditioning chemotherapy * Active infection, HIV infection, syphilis serology reaction positive; * Active hepatitis B, hepatitis C at the time of screening * Significant hepatic dysfunction as following, SGOT(serum glutamic-oxaloacetic transaminase)\> 5 x upper limit of normal; bilirubin \> 3.0 mg/dL; * Lymphotoxic chemotherapeutic agents within 2 weeks of leukapheresis * serious mental disorder; * With severe cardiac, liver, renal insufficiency, diabetes and other diseases; * Participate in other clinical research in the past three months; previously treatment with any gene therapy products * Contraindication to cyclophosphamide or fludarabine chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to 90 days after T cell infusion | Proportion of patients in whom a response among complete response or partial response, as defined by International Myeloma Working group(IMWG) response criteria , will be observed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability | Up to 35 days after T cell infusion | Adverse events assessed according to NCI-CTCAE v4.03 criteria |
| Duration of persistence of BCMA-UCART | Baseline up to 1 year | Detect the duration of BCMA-UCART after injection using FACS or Q-PCR |
Countries
China
Outcome results
None listed