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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05016778
Recruitment Status : Active, not recruiting
First Posted : August 23, 2021
Last Update Posted : November 1, 2022
Sponsor:
Collaborator:
OriCell Therapeutics Co., Ltd.
Information provided by (Responsible Party):
He Huang, Zhejiang University

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
Multiple Myeloma Drug: GPRC5D-CAR-T Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : June 8, 2021
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : June 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

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.




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

  2. AE and SAE [ Time Frame: 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 [ Time Frame: From admission to the end of the follow-up, up to 2 years ]
    In peripheral blood and bone marrow

  2. Objective Response Rate, ORR [ Time Frame: In 3 months of GPRC5D CAR-T cell infusion ]
    Proportion of subjects with complete or partial remission

  3. Disease control rate, DCR [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From GPRC5D CAR-T infusion to death,up to 2 years ]
    The time from the cell reinfusion to death due to any cause.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05016778


Locations
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China, Zhejiang
The first affiliated hospital of medical college of zhejiang university
Hangzhou, Zhejiang, China, 310003
Sponsors and Collaborators
Zhejiang University
OriCell Therapeutics Co., Ltd.
Investigators
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Principal Investigator: Huang He Hematology
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Responsible Party: He Huang, Chief Physician, Zhejiang University
ClinicalTrials.gov Identifier: NCT05016778    
Other Study ID Numbers: POLARIS
First Posted: August 23, 2021    Key Record Dates
Last Update Posted: November 1, 2022
Last Verified: October 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by He Huang, Zhejiang University:
CAR-T
GPRC5D
Multiple Myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases