A Study of CAR-GPRC5D in Patients With Relapsed/Refractory Multiple Myeloma or Plasma Cell Leukemia

Study Purpose

This study is a single-center, open, dose-escalation study to observe the safety and efficacy of different doses of CAR-GPRC5D in patients with R/R MM or plasma cell leukemia.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 75 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Subjects must satisfy all the following criteria to be enrolled in the study: 1.
age 18 to 75 years old, male or female. 2. Subjects have had at least 3 prior lines of therapy including chemotherapy based on proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). According to the International Myeloma Working Group (IMWG) consensus (2016) standard on multiple myeloma, the disease has recurred, progressed or is refractory, or according to the IMWG consensus (2013) standard on plasma cell leukemia (Appendix 4), the disease appears relapse, progress or refractory; 3. Evidence of cell membrane GPRC5D expression, as determined by a validated immunohistochemistry (IHC) or flow cytometry of tumor tissue (e.g., bone marrow biopsies, or plasmacytoma). 4. The subjects should have measurable disease based on at least one of the following parameters: The proportion of primitive immature or monoclonal plasma cells detected by bone marrow cytology, bone marrow biopsy, or flow cytometry is ≥ 10%. Serum M-protein ≥ 0.5 g/dL. Urine M-protein ≥ 200 mg/24 hrs. For those whose Serum or Urine M-protein does not meet the measurable criteria but the light chain type, serum free light chain (sFLC) : involved sFLC level ≥ 10mg/dL (100 mg/L) provided serum FLC ratio is abnormal. In subjects with extramedullary myeloma, if there are no other evaluable lesions, require extramedullary lesions with a maximum diameter of ≥2cm. 5. ECOG performance score 0-2. 6. Estimated life expectancy ≥ 12 weeks. 7. Subjects should have adequate organ function:
  • - Hematology: Absolute neutrophil count (ANC) ≥1×10^9 /L (prior use of growth factor support is permitted, but subjects must not have received supportive treatment within 7 days prior to laboratory examination); absolute lymphocyte count (ALC) ≥0.3×10^9 /L; platelets ≥40×10^9 /L (subjects must not have received blood transfusion support within 7 days prior to laboratory examination); hemoglobin ≥60 g/L (subjects must not have received transfusion of red blood cells [RBC] within 7 days prior to laboratory examination; the use of recombinant human erythropoietin is permitted).
  • - Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); total serum bilirubin ≤ 1.5×ULN.
  • - Renal function: Creatinine clearance rate (CrCl) calculated according to Cockcroft-Gault formula ≥ 40 ml/min.
  • - Coagulation function: Fibrinogen ≥ 1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, prothrombin time (PT) ≤1.5×ULN.
  • - SpO2 > 91%.
  • - Left ventricular ejection fraction (LVEF) ≥ 50%.
8. The subject and his/her spouse agree to use an effective contraceptive tool or medication (excluding safety period contraception) for one year from the date of the subject's informed consent to the date of CAR T cell infusion. 9. Subject must sign the informed consent form approved by ethics board in person before starting any screening procedure.

Exclusion Criteria:

  • - The presence of any of the following will exclude a subject from enrollment: 1.
Subjects who are known to have GVHD or need long-term immunosuppressive therapy. 2. Subjects have received any anti-cancer treatment as follows: monoclonal antibody for treating multiple myeloma within 21 days before leukapheresis, or cytotoxic therapy or proteasome inhibitors within 14 days before leukapheresis, or immunomodulatory agents within 7 days before leukapheresis. or anti-tumor treatments other than those listed above within 30 days before leukapheresis. 3. Subjects who were receiving a used therapeutic dose of corticosteroid treatment (defined as prednisone or equivalent > 20mg) within 7 days prior to screening, except for physiological alternatives, inhalation, or topical use. 4. Subjects with hypertension that cannot be controlled by medication. 5. Subjects with serious heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmias. 6. Subjects with systemic diseases that the investigator determined to be unstable include, but are not limited to, severe liver and kidney or metabolic diseases requiring medical treatment. 7. Subjects with second malignancies in addition to MM within the past 5 years before the screening, exceptions to this criterion: successfully treated cervical carcinoma in situ and non-metastatic basal or squamous cell skin carcinoma, local prostate cancer after radical surgery, and ductal carcinoma in situ of the breast after radical surgery. 8. Subjects with a history of organ transplantation. 9. Subjects have received major surgery within 2 weeks prior to leukapheresis or plan to receive surgery during the study or within 2 weeks after the study treatment (excluding local anesthesia). 10. Subjects participated in another interventional clinical study 1 months before signing the informed consent (ICF); 11. Subjects with any uncontrolled active infection needed to receive systemic therapy within 7 days before leukapheresis collection (excluding # CTCAE grade 2 urogenital infection and upper respiratory infection). 12. Positive for any of the following tests:
  • - Hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis B core antibody-positive and detectable HBV DNA in peripheral blood.
  • - Hepatitis C virus (HCV) antibody and hepatitis C virus RNA in peripheral blood.
  • - Human immunodeficiency virus (HIV) antibody.
  • - Cytomegalovirus (CMV) DNA.
  • - Treponema Pallidum antibody.
13. Pregnant or lactating women. 14. Subjects with mental illness or consciousness disorder or disease of the central nervous system. 15. Other conditions that researchers consider inappropriate for inclusion.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05219721
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Chunrui Li
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Chunrui Li
Principal Investigator Affiliation Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries China
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Relapsed/Refractory Multiple Myeloma, Plasma Cell Leukemia
Additional Details

Leukapheresis procedure will be performed to manufacture CAR-GPRC5D chimeric antigen receptor (CAR) modified T cells. Bridging therapy is allowed between PBMC collection and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide was performed for three consecutive days. After 1-day rest, subjects will receive a single dose infusion of CAR-GPRC5D at 0.5, 1.0, or 2.0 x 10^6 CAR+ T cells/Kg. Subjects will be followed in the study for a minimum of 2 years after infusion. Long-term follow-up for lentiviral vector safety will be followed for up to 15 years after infusion.

Arms & Interventions

Arms

Experimental: CAR-GPRC5D cells

The tolerability and safety of CAR-GPRC5D cells will be assessed according to the "3+3" dose-escalation design. There will be three dose levels, 0.5×10^6, 1.0×10^6, and 2.0×10^6, CAR+T cells/kg. For each level, 3-6 subjects will be enrolled.

Interventions

Drug: - CAR-T (CAR-GPRC5D)

CAR-GPRC5D is an individualized, gene-modified autologous T cell immunotherapy product targeting GPRC5D that identifies and eliminates malignant and normal cells expressing GPRC5D. CAR specifically recognizes GPRC5D with a hypoimmunogenic human single-chain variable fragment (ScFv) that promotes car-T activation, proliferation, cytokine secretion and target cell killing through the CD3ζ domain. The amplification and persistence of CAR T are enhanced by 4-1BB costimulation signal.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Wuhan, Hu Bei, China

Status

Recruiting

Address

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hu Bei, 430000

Site Contact

Chunrui Li

cunrui5650@126.com

+86 13647233185