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

NCT03380039 | Unknown DMC

• 1 other identifier: XH-17-018
• Study Type: interventional
• Target: 6
• 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 (1)

• Number of participants with CAR-BCMA T cell therapy-related adverse events as assessed by CTCAE v4.03

  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.

  24 weeks

Secondary Outcomes (6)

• Engraftment

  2 years

• Anti-tumor response of CAR-BCMA T cell infusion

  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

Other Outcomes (3)

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

  2 years

• Anti-drug antibody

  2 years

• Changes of cell subsets of CAR-BCMA T cells against T cells

  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;
• \) 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);
• \- iii. 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);
• \- iv. Bone marrow plasma cell percentage increases ≥ 25% (absolute increase should be ≥ 10%);
• \- v. Size of existing bone lesions or soft tissue plasmacytomas increases by ≥ 25%, or development of new lytic bone lesions or soft tissue plasmacytomas;
• \- vi. Development of hypercalcemia that can be attributed to plasma cell proliferative disorder (corrected calcium is \> 2.8 mmol/L or 11.5 mg/dL);
• \- vii. Disease progression must be confirmed by 2 sequential assessments.

You may not qualify if:

• 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.
• 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, 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

• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: lead
• CARsgen Therapeutics Co., Ltd.: collaborator

Study Sites (1)

Xin Hua Hospital of Shanghai Jiao Tong University of Medicine

Shanghai, Shanghai Municipality, 200092, 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

• Siguo Hao, MD

  Xin Hua Hospital of Shanghai Jiao Tong University of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2017
• First Posted: December 20, 2017
• Study Start: October 13, 2017
• Primary Completion: July 2, 2020
• Study Completion: July 2, 2023
• Last Updated: October 12, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)