A Clinical Study to Evaluate the Safety and Efficacy of BCMA-GPRC5D CAR-T in Patients With Relapsed/Refractory Multiple Myeloma Who Received Three or More Lines of Therapy

NCT05998928 | Recruiting Phase 2

• 1 other identifier: BCMA-GPRC5D CAR-T-cells
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of bispecific BCMA-GPRC5D Chimeric antigen receptor (CAR) T-cells in patients with relapsed or refractory multiple myeloma who received three or more lines of therapy.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-related Adverse Events

  Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome are graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Other therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)

  within 2 years after infusion

Secondary Outcomes (14)

• Pharmacokinetics and pharmacodynamics - Cmax

  within 2 years after infusion

• Pharmacokinetics and pharmacodynamics - Tmax

  within 2 years after infusion

• Pharmacokinetics and pharmacodynamics - AUC 0-28d

  within 2 years after infusion

• Pharmacokinetics and pharmacodynamics - AUC 0-90d

  within 2 years after infusion

• Pharmacokinetics and pharmacodynamics - AUC 0-inf

  within 2 years after infusion

Study Arms (1)

Fludarabine + Cyclophosphamide + BCMA-GPRC5D CAR-T Cells

EXPERIMENTAL

Patients will receive lymphodepletion chemotherapy with fludarabine (30 mg/m2 body surface area) plus cyclophosphamide (300 mg/m2 body surface area) for 3 consecutive days during D-7 to D-3, followed by the infusion of BCMA-GPRC5D CAR-T cells at a single dose of 4.0×10\^6/kg ± 50%/kg for one day.

Drug: Fludarabine + Cyclophosphamide + BCMA-GPRC5D CAR-T Cells

Interventions

Fludarabine + Cyclophosphamide + BCMA-GPRC5D CAR-T Cells DRUG

fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 both on three consecutive days during D-7 to D-3 BCMA-GPRC5D CAR-T Cells on day 0

Fludarabine + Cyclophosphamide + BCMA-GPRC5D CAR-T Cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient or his or her legal guardian voluntarily participates in and signs an informed consent form;
• Aged ≥ 18 years and ≤ 75 years;
• Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG);
• The presence of measurable disease at screening meets one of the following criteria:Serum M-protein ≥ 1.0 g/dL or Urine M-protein ≥ 200 mg/24h or diagnosed as Light-chain MM without measurable disease in serum and urine; Serum free light chain ≥ 10 mg/dL with an abnormal κ/λ ratio;
• Patients must relapse or be refractory after three or more lines of therapy, which at least include: one Proteasome Inhibitor (PI), one Immunomodulatory Drug (IMiD), and one anti-CD38 monoclonal antibody;
• diagnosed as relapsed/refractory disease or primary refractory disease;
• The last treatment is ineffective, or the disease progresses within 60 days after the end of the last therapy;
• Patients must recover from the toxicity of the last therapy (\< grade 2 by CTCAE criteria);
• ECOG score 1-2 points and the expected survival period ≥ 3 months;
• Liver, kidney and cardiopulmonary functions meet the following requirements:
• Total bilirubin ≤ 1.5×ULN, alanine aminotransferase (ALT) ≤ 3 × ULN and aspartate aminotransferase (AST) ≤ 3 × ULN;
• Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 60 mL/min;
• Hemoglobin (Hb) ≥ 50 g/L without prior blood transfusion within 7 days;
• Baseline peripheral oxygen saturation \> 92%;
• Corrected serum calcium ≤ 12.5 mg/dL (≤ 3.1 mmol/L) or free (ionized, ionic) calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L);

You may not qualify if:

• Previous diagnosis and treatment of other malignancies within 3 years;
• Patients received previous anti-tumor therapies before apheresis including following therapies: targeted therapies, epigenetics modulation drugs, other drugs or medical devices (invasive) of clinical trials, monoclonal antibodies, cytotoxic agents, PIs, IMiDs, radiotherapy;
• Central Nervous System (CNS) involvement;
• Patients with Fahrenheit macroglobulinemia, POEMS syndrome, or primary AL, amyloidosis;
• Subjects with positive HBsAg or HBcAb positive and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive; HIV antibody positive; CMV DNA titer is higher than the lower limit of detection of the research institution; EBV DNA titer is higher than the lower limit of detection of the research institution;
• Patients have a severe allergic history;
• Patiens have severe systemic diseases or poor cardiovascular, liver, kidney functions;
• Acute or chronic graft versus host disease (GvHD) occurs within 6 months before the screening or needs be treated with immunosuppressive agents;
• Active autoimmune or inflammatory diseases of the nervous system;
• Patients develop oncology emergencies and need to be treated before screening or infusion;
• Uncontrolled infections that need antibiotics treatment;
• Exposure to hematopoietic growth factor of cells within 1-2 weeks before apheresis;
• Exposure to Corticosteriods or immunosuppressive agents within 2 weeks before apheresis;
• Patients receive a major surgical operation within 4 weeks before lymphodepletion or do not recover completely before the enrollment; or plan to receive a major surgical operation during the study period;
• Live attenuated vaccine within 4 weeks before screening;

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Guangzhou Bio-gene Technology Co., Ltd: collaborator

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Related Publications (2)

• Mailankody S, Devlin SM, Landa J, Nath K, Diamonte C, Carstens EJ, Russo D, Auclair R, Fitzgerald L, Cadzin B, Wang X, Sikder D, Senechal B, Bermudez VP, Purdon TJ, Hosszu K, McAvoy DP, Farzana T, Mead E, Wilcox JA, Santomasso BD, Shah GL, Shah UA, Korde N, Lesokhin A, Tan CR, Hultcrantz M, Hassoun H, Roshal M, Sen F, Dogan A, Landgren O, Giralt SA, Park JH, Usmani SZ, Riviere I, Brentjens RJ, Smith EL. GPRC5D-Targeted CAR T Cells for Myeloma. N Engl J Med. 2022 Sep 29;387(13):1196-1206. doi: 10.1056/NEJMoa2209900.

  PMID: 36170501 BACKGROUND

• Fernandez de Larrea C, Staehr M, Lopez AV, Ng KY, Chen Y, Godfrey WD, Purdon TJ, Ponomarev V, Wendel HG, Brentjens RJ, Smith EL. Defining an Optimal Dual-Targeted CAR T-cell Therapy Approach Simultaneously Targeting BCMA and GPRC5D to Prevent BCMA Escape-Driven Relapse in Multiple Myeloma. Blood Cancer Discov. 2020 Sep;1(2):146-154. doi: 10.1158/2643-3230.BCD-20-0020.

  PMID: 33089218 BACKGROUND

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

• Heng Mei

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heng Mei

CONTACT

027-8572600; hmei@hust.edu.cn

Chenggong Li

CONTACT

18108675948; chenggongli@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Proferssor, Cheif Doctor

Study Record Dates

• First Submitted: July 28, 2023
• First Posted: August 21, 2023
• Study Start: July 27, 2023
• Primary Completion: July 27, 2025
• Study Completion (Estimated): July 27, 2026
• Last Updated: November 13, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)