Clinical Study of Redirected Autologous T Cells With a BCMA-targeted Chimeric Antigen Receptor in Patients With Refractory or Relapsed Multiple Myeloma
Overview
- Phase
- Not Applicable
- Intervention
- CAR-BCMA T cells
- Conditions
- Refractory or Relapsed Multiple Myeloma
- Sponsor
- Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Number of participants with CAR-BCMA T cell therapy-related adverse events as assessed by CTCAE v4.03
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Detailed Description
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 changes of cell subsets of CAR-BCMA T cells against T cells (Tcm, central memory T lymphocytes; Tem, effector memory T lymphocytes; Treg, regulatory T lymphocytes).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients aged between 18 \~ 70 with relapsed or refractory multiple myeloma.
- •Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination.
- •Patients with relapsed or refractory multiple myeloma who meet the following conditions:
- •Curative efficacy is little or disease progressed after 2 courses of standard treatment regimen;
- •Disease relapsed after chemotherapy or HSCT. Curative efficacy is little or disease progressed after 2 courses of original treatment regimen;
- •More than 60 days between last treatment and disease progression;
- •Autologous or allogeneic SCT is not available at present, or patient refuses to receive SCT;
- •Disease progression is defined as per "Chinese Guidelines for Diagnosis and Treatment of Multiple Myeloma (Revision in 2015)". At least one of the following conditions should be met:
- •- i. Serum M-protein increases ≥ 25% (absolute increase should be ≥ 5 g/L). If serum M protein is ≥ 50 g/L at baseline, increase of serum M protein can be ≥ 10 g/L;
- •- ii. Urine M-protein increases ≥ 25% (absolute increase should be ≥ 200 mg/24 h);
Exclusion Criteria
- •Patients with any of the following conditions are not eligible for this study.
- •Transduction of target lymphocytes \< 10%, expansion in response to αCD3/CD28 costimulation \< 5-fold.
- •Pregnant or lactating women.
- •HIV positive, or HCV positive
- •Uncontrolled active infection, including active tuberculosis and HBV DNA copies ≥ 1×10\^3 copies/mL.
- •Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
- •Allergic to immunotherapies and related drugs.
- •Patients with heart disease for which treatment is needed or with poorly controlled hypertension.
- •Hyponatremia: serum sodium level \< 125 mmol/L.
- •Baseline serum potassium \< 3.5 mmol/L (taking potassium supplements before participating in the study to raise potassium level is acceptable).
Arms & Interventions
CAR-BCMA T cells
In this study, autologous T cells transduced with a BCMA-targeted chimeric antigen receptor (CAR-BCMA T cells) are used to treat patients with refractory or relapsed multiple myeloma. Route of administration: Intravenous injection. Lymphodepletion conditioning: Lymphodepletion will be conducted several days prior to CAR-BCMA T cells infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
Intervention: CAR-BCMA T cells
CAR-BCMA T cells
In this study, autologous T cells transduced with a BCMA-targeted chimeric antigen receptor (CAR-BCMA T cells) are used to treat patients with refractory or relapsed multiple myeloma. Route of administration: Intravenous injection. Lymphodepletion conditioning: Lymphodepletion will be conducted several days prior to CAR-BCMA T cells infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
Intervention: Fludarabine
CAR-BCMA T cells
In this study, autologous T cells transduced with a BCMA-targeted chimeric antigen receptor (CAR-BCMA T cells) are used to treat patients with refractory or relapsed multiple myeloma. Route of administration: Intravenous injection. Lymphodepletion conditioning: Lymphodepletion will be conducted several days prior to CAR-BCMA T cells infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
Intervention: Cyclophosphamide
Outcomes
Primary Outcomes
Number of participants with CAR-BCMA T cell therapy-related adverse events as assessed by CTCAE v4.03
Time Frame: 24 weeks
Number of participants with 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.
Secondary Outcomes
- Engraftment(2 years)
- Statistical parameter of efficacy assessment#PFS(5 years)
- Statistical parameter of efficacy assessment#DCR(2 years)
- Statistical parameter of efficacy assessment#ORR(2 years)
- Statistical parameter of efficacy assessment#OS(5 years)
- Anti-tumor response of CAR-BCMA T cell infusion(2 years)