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

NCT03716856 | Unknown Phase 1

• 1 other identifier: CG6003
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Refractory or Relapsed Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

• 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

Other Outcomes (3)

• Number of DNA copies of CAR-BCMA T cells in tissue samples

  2 years

• Positive incidence of anti-drug antibody

  2 years

• Change of T cell subsets from baseline counts

  2 years

Study Arms (1)

CAR-BCMA T cells

EXPERIMENTAL

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.

Genetic: CAR-BCMA T cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

CAR-BCMA T cells GENETIC

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

Also known as: BCMA-redirected autologous T cells

CAR-BCMA T cells

Fludarabine DRUG

Fludarabine is used for lymphodepletion.

CAR-BCMA T cells

Cyclophosphamide DRUG

Cyclophosphamide is used for lymphodepletion

CAR-BCMA T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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;
• 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%.

You may not qualify if:

• 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.
• 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.).

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• CARsgen Therapeutics Co., Ltd.: collaborator

Study Sites (1)

First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310006,, China

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Jie Jin, MD

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

• Haitao Meng, MD

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2018
• First Posted: October 23, 2018
• Study Start: March 23, 2018
• Primary Completion: June 23, 2020
• Study Completion: June 23, 2023
• Last Updated: October 8, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)