Safety and Efficacy of Anti-BCMA/GPRC5D CAR-T Cell Therapy in Treating Relapsed and Refractory Multiple Myeloma(rr/MM)

NCT05509530 | Unknown Phase 2 DMC

• 1 other identifier: XYFY2022-KL118-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, single-arm, Phase 2 study to evaluate the efficacy and safety of Anti-BCMA/GPRC5D CAR-T in subjects with relapsed and refractory multiple myeloma. A leukapheresis procedure will be performed to manufacture Anti-BCMA/GPRC5D chimeric antigen receptor (CAR) modified T cells. Prior to Anti-BCMA/GPRC5D infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; BCMA; GPRC5D

Outcome Measures

Primary Outcomes (1)

• Number of participants with Adverse Events, with abnormal vital signs, abnormal physical examination findings, abnormal laboratory test results, abnormal ECGs and abnormal echocardiograms.

  12 months

Secondary Outcomes (4)

• overall response rate (ORR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for MM

  24 months

• complete response (CR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for MM

  24 months

• very good partial response (VGPR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for MM

  24 months

• partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for MM

  24 months

Study Arms (1)

anti BCMA/GPRC5D CAR-T

EXPERIMENTAL

Enrolled patients will receive prespecified dose of autologous anti BCMA/GPRC5D CAR-T cells.

Other: anti-BCMA/GPRC5D CAR-T CELL

Interventions

anti-BCMA/GPRC5D CAR-T CELL OTHER

anti-BCMA/GPRC5D autologous CAR T cells will be infused at a dose ranging from 1 - 2 x 10\^6/kg CAR+ T cells after receiving lymphodepleting chemotherapy

anti BCMA/GPRC5D CAR-T

Eligibility Criteria

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

You may qualify if:

• Age and gender: 18 years old \<= age \<= 70 years old, gender unlimited, signing informed consent voluntarily;
• According to the classification definition of IMWG standard, the diagnosis of plasmacytoma is multiple myeloma, plasmacytic leukemia, poems syndrome, monoclonal IMMUNOGLOBULINEMIA, primary macroglobulinemia or primary amyloidosis which are invalid or relapsed after at least three-line treatment (including chemotherapy based on bortezomib and / or lenalidomide);
• BCMA and GPRC5D were positive on the surface of plasma membrane;
• The patients could not receive the treatment of HSCT, or the relapse after HSCT was judged to need treatment by researchers;
• ECOG score is 0 or 1;
• Expected survival time \>= 12 weeks;
• The subjects must have proper organ function and meet all the following laboratory test results before entering the group
• Blood routine test: neutrophil \>= 1.0 x 10\^9 / L; hemoglobin \>= 70 g / L; platelet \>= 50 x 10\^9 / L;
• Liver function: ALT and AST \<= 2.5 x ULN; total bilirubin \<= 1.5 x ULN;
• Renal function: serum creatinine \<= 2.5 x ULN; or creatinine clearance calculated according to Cockcroft Gault formula Rate CrCl \>= 60 ml / min.
• Electrolyte: blood potassium \>= 3.0 mmol / L; blood calcium \>= 2.0 mmol / L; blood magnesium \>= 0.5 mmol / L;
• Coagulation function: fibrinogen \>= 1.0g/l; activated partial thromboplastin time (APTT) \<= Keywords ULN + 10s; prothrombin time (PT) \< ULN + 3S;
• The subjects should be willing to provide effective diagnosis evidence or bone marrow examination before treatment, and bone marrow or effective examination after treatment;
• Women of childbearing age and fertile male subjects must take one of the following effective contraceptive measures from signing informed consent until one year after anti-BCMA/GPRC5D CAR-T cell transfusion: abstinence, double barrier contraceptive method, IUD, hormone contraceptive;
• Male subjects were forbidden to donate sperm from signing the informed consent until one year after anti-BCMA/GPRC5D CAR-T cell transfusion;

You may not qualify if:

• Previous treatment history
• Received hematopoietic stem cell transplantation within 2 months before the start of administration, or within the screening period after transplantation, immunosuppressive therapy was used because of graft-versus-host disease;
• Patients who had received chemotherapy, immunotherapy, radiotherapy and major surgery within 4 weeks before the start of administration;
• Those who received the live vaccine within 4 weeks before the start of administration and / or planned to receive the live vaccine after the trial;
• Those who have received clinical trial drug treatment or are participating in other clinical trials within 4 weeks before drug administration;
• History of disease and operation
• Patients with central nervous system invasion by plasmacytoma;
• Hypertension and drug treatment can not get good control (blood pressure \> 140 / 90 mmHg);
• Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) \< 50%;
• Arrhythmia with NCI CTCAE 5.0 grade \>= 2, or male QTc \> 450 ms, female QTc \> 470 MS (QTc was calculated by the friderica correction formula QTc = QT / rr0.33); patients with a history of tip torsion or congenital QT prolongation syndrome;
• Patients with any of the following diseases within 12 months before administration: myocardial infarction, severe or unstable heart, patients with colic, coronary artery bypass or peripheral artery bypass grafting, congestive heart failure, cerebrovascular events (including transient ischemic attack), etc;
• During the screening period, the researchers judged that there were uncontrollable and active infectious diseases;
• People infected with human immunodeficiency virus (HIV);
• HBsAg was positive and in the active phase of hepatitis B (HBV DNA quantity \>= 1.00 x 10\^2 copies / ml);
• Hepatitis C antibody (anti HCV) was positive and was in the active phase of hepatitis C (hepatitis C RNA was not in the normal mode)Perimetric value);

Sponsors & Collaborators

• Xuzhou Medical University: lead

Study Sites (1)

Kailin Xu

Xuzhou, Jiangsu, 221000, China

RECRUITING

Related Publications (1)

• Zhou D, Sun Q, Xia J, Gu W, Qian J, Zhuang W, Yan Z, Cheng H, Chen W, Zhu F, Qi K, Li D, Sang W, Zhu L, Ma S, Li H, Zhang H, Qiu T, Yan D, Zhang Y, Peng S, Chang AH, Xu K, Li Z. Anti-BCMA/GPRC5D bispecific CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, single-centre, phase 1 trial. Lancet Haematol. 2024 Oct;11(10):e751-e760. doi: 10.1016/S2352-3026(24)00176-5. Epub 2024 Jul 23.

  PMID: 39059405 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

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

Study Officials

• Kailin Xu, M.D., Ph.D.

  Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kailin Xu, M.D., Ph.D.

CONTACT

15162166166; lihmd@163.com

Junnian Zheng, M.D., Ph.D.

CONTACT

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: Principal Investigator

Study Record Dates

• First Submitted: August 2, 2022
• First Posted: August 22, 2022
• Study Start: May 1, 2022
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: August 22, 2022

Record last verified: 2022-08

Locations

CN (1)