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

NCT ID: NCT05016778

Last Updated: 2022-11-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-08
• Study Completion Date: 2025-06-30

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Group

This is a open label, single arm clinical trial.

Group Type: EXPERIMENTAL

GPRC5D-CAR-T

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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:

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

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

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

4. Or there are extramedullary lesions;

7. 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 ;

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

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

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

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

12. The blood routine meets the following standards:

1. Lymphocyte count>0.5×10e9/L;

2. Neutrophils ≥1.0×10e9/L;

3. Hemoglobin ≥80g/L;

4. Platelet ≥75×10e9/L

13. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

OriCell Therapeutics Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

He Huang

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Huang He

Role: PRINCIPAL_INVESTIGATOR

Hematology

Locations

The first affiliated hospital of medical college of zhejiang university

Hangzhou, Zhejiang, China

Countries

China

References

Zhang M, Wei G, Zhou L, Zhou J, Chen S, Zhang W, Wang D, Luo X, Cui J, Huang S, Fu S, Zhou X, Tang Y, Ding X, Kuang J, He XP, Hu Y, Huang H. GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-centre, single-arm, phase 1 trial. Lancet Haematol. 2023 Feb;10(2):e107-e116. doi: 10.1016/S2352-3026(22)00372-6.

Reference Type: DERIVED

PMID: 36725117 (View on PubMed)

Other Identifiers

POLARIS

Identifier Type: -

Identifier Source: org_study_id