A single arm, open-label pilot study is designed to determine the safety, efficacy and cytokinetics of CAR-BCMA T cells in patients with BCMA-positive refractory or relapsed multiple myeloma.
This study is designed to determine the safety, tolerability and engraftment potential of anti-BCMA lentivirus-transduced autologous T cells in patients with refractory or relapsed multiple myeloma. Primary objectives: 1. Determine the safety and tolerability of CAR-BCMA T cells (autologous T cells transduced with chimeric antigen receptors recognizing BCMA) in patients with refractory or relapsed multiple myeloma. 2. Observe the cytokinetics of CAR-BCMA T cells. Secondary objectives: 1. Observe the anti-tumor response of CAR-BCMA T cells to refractory or relapsed multiple myeloma (evaluated by diagnostic criteria International Myeloma Working Group (IMWG2014 version) as CR, sCR, ICR, MCR or VGPR). 2. Make an evaluation on the distribution and in vivo survival of CAR-BCMA T cells in peripheral blood, lymph node, and bone marrow. 3. Observe the immunogenicity of CAR-BCMA T cells, and determine if there is anti-BCMA scFv cellular immune response and anti-BCMA scFv humoral immune response. 4. Observe the change of T cell subsets relative to CAR-BCMA T。 (Tcm, central memory T lymphocytes; Tem, effector memory T lymphocytes; Treg, regulatory T lymphocytes).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Single dose of CAR-BCMA T cells will be infused, and classic "3+3" dose escalation will be applied.
Fludarabine is used for lymphodepletion.
Cyclophosphamide is used for lymphodepletion
First Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang, China
Safety and effectivity - Incidence of study related adverse events
Incidence of study related adverse events which are defined as laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the infusion until week 24, including infusion related toxicity and any toxicity possibly related to CAR-BCMA T cells.
Time frame: 24 weeks
Engraftment
Duration of in vivo survival of CAR-BCMA T cells is defined as "engraftment". After 24 hours of infusion, the CAR-BCMA DNA sequence was detected by PCR according to the follow-up time point, until the result of any two consecutive tests was negative and recorded as the "engraftment endpoint" of CAR-BCMA T cells.
Time frame: 2 years
Statistical parameter of efficacy assessment:PFS
Statistical parameter:Progression-free Survival (PFS)
Time frame: 5 years
Statistical parameter of efficacy assessment:DCR
Statistical parameter:Disease Control Rate (DCR)
Time frame: 2 years
Statistical parameter of efficacy assessment:ORR
Statistical parameter:Objective Remission Rate (ORR)
Time frame: 2 years
Statistical parameter of efficacy assessment:OS
Statistical parameter:Overall survival (OS)
Time frame: 5 years
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