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A Study of CAR-T Cells Targeting GPRC5D in the Treatment of r/r Multiple Myeloma

Sponsor
Zhejiang University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05016778
Collaborator
Oricell Therapeutics Co., Ltd (Other)
15
Enrollment
1
Location
1
Arm
48.7
Anticipated Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a single-arm, open-label, dose-escalation study to evaluate the safety, tolerability, cellular kinetics and initial efficacy of CAR-T cell therapy targeting GPRC5D in multiple myeloma subjects who have failed the standard treatments.

Condition or Disease Intervention/Treatment Phase
Early Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Single Arm, Open Label Clinical Study of CAR-T Cells Targeting GPRC5D in the Treatment of Relapsed / Refractory Multiple Myeloma(POLARIS)
Actual Study Start Date :
Jun 8, 2021
Anticipated Primary Completion Date :
Jun 30, 2024
Anticipated Study Completion Date :
Jun 30, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment Group

This is a open label, single arm clinical trial.

Drug: GPRC5D-CAR-T
After enrollment, subjects complete the PBMC apheresis, then complete the Lymphocyte clearance, and then receive the dose climbing test: 1×10e6/kg，3×10e6/kg，6×10e6/kg.

Outcome Measures

Primary Outcome Measures

  1. Dose limited toxicity (DLT) [From date of initial treatment to Day 28 post GPRC5D CAR-T infusion.]

    Dose limited toxicity

  2. AE and SAE [From admission to the end of the follow-up, up to 2 years]

    Adverse event and serious adverse event

Secondary Outcome Measures

  1. Concentration of CAR-T cells [From admission to the end of the follow-up, up to 2 years]

    In peripheral blood and bone marrow

  2. Objective Response Rate, ORR [In 3 months of GPRC5D CAR-T cell infusion]

    Proportion of subjects with complete or partial remission

  3. Disease control rate, DCR [From Day 28 GPRC5D CAR-T infusion up to 2 years]

    The percentage of patients with remission and stable disease after treatment in the total evaluable cases.

  4. Duration of remission, DOR [24 months post GPRC5D CAR-T cells infusion]

    The time from the first assessment of remission or partial remission of the tumor to the first assessment of disease progression or death from any cause;

  5. Progression-free survival, PFS [24 months post GPRC5D CAR-Tcells infusion]

    The time from cell reinfusion to the first assessment of tumor progression or death from any cause

  6. Overall survival, OS [From GPRC5D CAR-T infusion to death，up to 2 years]

    The time from the cell reinfusion to death due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. The subject can understand and have the ability to sign an informed consent form;

  2. Male or female subjects, aged 18-75 years;

  3. The expected survival period is not less than 12 weeks;

  4. ECOG score ≤ 2 ;

  5. Diagnosed as multiple myeloma according to the IMWG standard in 2018;

  6. The expression of GPRC5D in bone marrow plasma cells is more than 20%, or it is positive in tumor tissue by immunohistochemistry. One of the following criteria must be detected:

  7. If IgG type MM, serum M protein ≥10g/L; if IgA, IgD, IgE or IgM type MM, serum M protein ≥5g/L;

  8. Or urine M protein level ≥200mg/24h;

  9. Or light chain type MM, serum free light chain (sFLC) ≥ 100mg / L and K/ λ FLC ratio is abnormal;

  10. Or there are extramedullary lesions;

  11. Subjects who have received at least 3 different mechanism drugs (including chemotherapy, protease inhibitors, immunosuppressive agents, etc.) have failed treatments, or have progressed or recurred during the last treatment or within 6 months after the end of treatment ;

  12. Lung function is normal, and oxygen saturation is greater than 92%;

  13. No heart disease or coronary heart disease, echocardiogram showed normal diastolic function, left ventricular ejection fraction (LVEF) ≥50%, and no serious arrhythmia;

  14. Liver function: TBIL<3×ULN, AST<2.5×ULN, ALT<2.5ULN;

  15. Renal function: creatinine clearance rate (estimated by Cockcroft Gault formula) ≥ 30 mL/min;

  16. The blood routine meets the following standards:

  17. Lymphocyte count>0.5×10e9/L;

  18. Neutrophils ≥1.0×10e9/L;

  19. Hemoglobin ≥80g/L;

  20. Platelet ≥75×10e9/L

  21. From the use of study drug to 2 years after treatment, male subjects or female subjects of childbearing age must agree and be able to take effective contraceptive measures.

Exclusion Criteria:

  1. Pregnant or breastfeeding;

  2. HBsAg or HBcAb are positive, and the quantitative detection of HBV DNA in peripheral blood is more than 100 copies / L; HCV antibody and HCV RNA in peripheral blood are positive; HIV antibody positive; Syphilis antibody is positive in the first screening;

  3. Any unstable systemic disease: including but not limited to unstable angina, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ grade III), severe arrhythmia with poor drug control, liver, kidney or metabolic diseases;

  4. Had hypersensitivity or intolerance to any drug used in this study;

  5. Patients who received anti-cancer chemotherapy or other medications within 2 weeks before screening;

  6. Uncontrolled malignant tumors except MM, excluding malignant tumors that received radical treatment and no active disease was found within 3 years before enrollment;

  7. Clinically significant central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, psychosis, active central nervous system involvement or cancerous meningitis;

  8. In the past two years, autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) caused damage to terminal organs, or required systemic application of immunosuppressive or other drugs;

  9. Severe active viral, bacterial or uncontrolled systemic fungal infections; Hereditary bleeding / coagulation diseases, history of non traumatic bleeding or thromboembolism, other diseases that may increase the risk of bleeding, etc;

  10. Patients who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks before screening, or who plan to undergo ASCT during the study period;

  11. Patients received allogeneic stem cell therapy;

  12. Any unsuitable to participate in this trial judged by the investigator.

Contacts and Locations

Locations

Site City State Country Postal Code
1 The first affiliated hospital of medical college of zhejiang university Hangzhou Zhejiang China 310003

Sponsors and Collaborators

  • Zhejiang University
  • Oricell Therapeutics Co., Ltd

Investigators

  • Principal Investigator: Huang He, Hematology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
He Huang, Chief Physician, Zhejiang University
ClinicalTrials.gov Identifier:
NCT05016778
Other Study ID Numbers:
  • POLARIS
First Posted:
Aug 23, 2021
Last Update Posted:
Apr 20, 2022
Last Verified:
Apr 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by He Huang, Chief Physician, Zhejiang University
CAR-T
GPRC5D
Multiple Myeloma
Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell

Study Results

No Results Posted as of Apr 20, 2022