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

NCT05016778 | Unknown Early Phase 1

• 1 other identifier: POLARIS
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Keywords

CAR-T; GPRC5D; Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Dose limited toxicity (DLT)

  Dose limited toxicity

  From date of initial treatment to Day 28 post GPRC5D CAR-T infusion.

• AE and SAE

  Adverse event and serious adverse event

  From admission to the end of the follow-up, up to 2 years

Secondary Outcomes (6)

• Concentration of CAR-T cells

  From admission to the end of the follow-up, up to 2 years

• Objective Response Rate, ORR

  In 3 months of GPRC5D CAR-T cell infusion

• Disease control rate, DCR

  From Day 28 GPRC5D CAR-T infusion up to 2 years

• Duration of remission, DOR

  24 months post GPRC5D CAR-T cells infusion

• Progression-free survival, PFS

  24 months post GPRC5D CAR-Tcells infusion

Study Arms (1)

Treatment Group

EXPERIMENTAL

This is a open label, single arm clinical trial.

Drug: GPRC5D-CAR-T

Interventions

GPRC5D-CAR-T 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.

Treatment Group

Eligibility Criteria

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

You may qualify if:

• The subject can understand and have the ability to sign an informed consent form;
• Male or female subjects, aged 18-75 years;
• The expected survival period is not less than 12 weeks;
• ECOG score ≤ 2 ;
• Diagnosed as multiple myeloma according to the IMWG standard in 2018;
• 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:
• If IgG type MM, serum M protein ≥10g/L; if IgA, IgD, IgE or IgM type MM, serum M protein ≥5g/L;
• Or urine M protein level ≥200mg/24h;
• Or light chain type MM, serum free light chain (sFLC) ≥ 100mg / L and K/ λ FLC ratio is abnormal;
• Or there are extramedullary lesions;
• 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 ;
• Lung function is normal, and oxygen saturation is greater than 92%;
• No heart disease or coronary heart disease, echocardiogram showed normal diastolic function, left ventricular ejection fraction (LVEF) ≥50%, and no serious arrhythmia;
• Liver function: TBIL\<3×ULN, AST\<2.5×ULN, ALT\<2.5ULN;
• Renal function: creatinine clearance rate (estimated by Cockcroft Gault formula) ≥ 30 mL/min;

You may not qualify if:

• Pregnant or breastfeeding;
• 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;
• 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;
• Had hypersensitivity or intolerance to any drug used in this study;
• Patients who received anti-cancer chemotherapy or other medications within 2 weeks before screening;
• Uncontrolled malignant tumors except MM, excluding malignant tumors that received radical treatment and no active disease was found within 3 years before enrollment;
• Clinically significant central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, psychosis, active central nervous system involvement or cancerous meningitis;
• 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;
• 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;
• Patients who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks before screening, or who plan to undergo ASCT during the study period;
• Patients received allogeneic stem cell therapy;
• Any unsuitable to participate in this trial judged by the investigator.

Sponsors & Collaborators

• Zhejiang University: lead
• OriCell Therapeutics Co., Ltd.: collaborator

Study Sites (1)

The first affiliated hospital of medical college of zhejiang university

Hangzhou, Zhejiang, 310003, China

Location

Related Publications (1)

• 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.

  PMID: 36725117 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

• Huang He

  Hematology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: June 6, 2021
• First Posted: August 23, 2021
• Study Start: June 8, 2021
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2025
• Last Updated: November 1, 2022

Record last verified: 2022-10

Locations

CN (1)