Clinical Study of CAR-BCMA T in Patients With Refractory or Relapsed Multiple Myeloma

Refractory or Relapsed Multiple Myeloma Clinical Trial

Official title:

Clinical Study of Redirected Autologous T Cells With a BCMA-targeted Chimeric Antigen Receptor in Patients With Refractory or Relapsed Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03716856
• Other study ID #: CG6003
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 23, 2018
• Est. completion date: June 23, 2023

Study information

• Verified date: September 2020
• Source: First Affiliated Hospital of Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 change of T cell subsets relative to CAR-BCMA T。 (Tcm, central memory T lymphocytes; Tem, effector memory T lymphocytes; Treg, regulatory T lymphocytes).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11
• Est. completion date: June 23, 2023
• Est. primary completion date: June 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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:

1. Curative efficacy is little or disease progressed after 2 courses of standard treatment regimen;

2. Disease relapsed after chemotherapy or HSCT. Curative efficacy is little or disease progressed after 2 courses of original treatment regimen;

3. More than 60 days between last treatment and disease progression;

4. Autologous or allogeneic SCT is not available at present, or patient refuses to receive SCT;

5. No response to treatment is defined according to International Myeloma Working Group 2014 version as not achieving CR (including CR, sCR, ICR, MCR) or PR (including VGPR, PR, MR) after 2 consecutive cycles of treatment with current therapy, and the interval between the 2 cycles is no more than 60 days. 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: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; Urine M-protein increases = 25% (absolute increase should be = 200 mg/24 h); If the serum and urine M-protein are not detectable, a = 25% increase in the difference between involved and uninvolved FLC levels is required (absolute increase should be = 100 mg/L); Bone marrow plasma cell percentage increases = 25% (absolute increase should be = 10%); Size of existing bone lesions or soft tissue plasmacytomas increases by = 25%, or development of new lytic bone lesions or soft tissue plasmacytomas; Development of hypercalcemia that can be attributed to plasma cell proliferative disorder (corrected calcium is > 2.8 mmol/L or 11.5 mg/dL); Disease progression must be confirmed by 2 sequential assessments.

• Expected survival > 12 weeks.

• Disease is measurable, and at least one of the following conditions should be satisfied:

• Serum M-protein is = 10 g/L;

• 24-hour urine M-protein is = 200 mg;

• Serum FLC is = 5 mg/dL;

• Plasmacytomas that can be evaluated by tests or imaging;

• Bone marrow plasma cell percentage is = 20%.

• ECOG scores 0 - 1.

• Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis.

• WBC = 1.5×10^9/L;PLT = 45×10^9/L; Hb=9.0g/dL

• Serum creatinine = 1.5 ULN.

• ALT = 2.5 ULN;AST = 2.5 ULN. The above lab results should not include those obtained from continuous supportive treatment that is ongoing.

Exclusion Criteria:

Patients with any of the following conditions are not eligible for this study.

• 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).

• Previous treatment with chemoradiotherapy, local treatment ,immunotherapy and tumor-targeting drug conducted 2 weeks prior to participation in this study or blood collection.

• Patients have undertaken immunosuppressor for graft-versus-host disease (GVHD) within 4 weeks before participation in this study or blood collection, or the patient is diagnosed with acute or chronic GVHD.

• Other severe disease that may restrain patients from participating in this study (e.g. diabetes, severe cardiac dysfunction, myocardial infarction or unstable arrhythmias or unstable angina in recent 6 months, gastric ulcer, active autoimmune disease, etc.).

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory or Relapsed Multiple Myeloma

Intervention

Genetic:
• CAR-BCMA T cells
Single dose of CAR-BCMA T cells will be infused, and classic "3+3" dose escalation will be applied.

Drug:
• Fludarabine
Fludarabine is used for lymphodepletion.
• Cyclophosphamide
Cyclophosphamide is used for lymphodepletion

Locations

Country	Name	City	State
China	First Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
First Affiliated Hospital of Zhejiang University	Carsgen Therapeutics, Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of DNA copies of CAR-BCMA T cells in tissue samples	Number of DNA copies of CAR-BCMA T cells in lymph node samples or bone marrow samples at regular intervals from 24 hours after the initial infusion.	2 years
Other	Positive incidence of anti-drug antibody	Positive incidence of anti-BCMA anti-drug antibody (ADA).	2 years
Other	Change of T cell subsets from baseline counts	Change of T cell subsets from baseline counts after infusion(Tcm, central memory T lymphocytes; Tem, effector memory T lymphocytes; Treg, regulatory T lymphocytes).	2 years
Primary	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.	24 weeks
Primary	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.	2 years
Secondary	Statistical parameter of efficacy assessment:PFS	Statistical parameter:Progression-free Survival (PFS)	5 years
Secondary	Statistical parameter of efficacy assessment:DCR	Statistical parameter:Disease Control Rate (DCR)	2 years
Secondary	Statistical parameter of efficacy assessment:ORR	Statistical parameter:Objective Remission Rate (ORR)	2 years
Secondary	Statistical parameter of efficacy assessment:OS	Statistical parameter:Overall survival (OS)	5 years