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

  • STATUS
    Recruiting
  • End date
    Mar 1, 2024
  • participants needed
    18
  • sponsor
    Chunrui Li
Updated on 5 June 2022
multiple myeloma
flow cytometry
ejection fraction
measurable disease
bone marrow procedure
refractory multiple myeloma

Summary

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.

Description

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.

Details
Condition Relapsed/Refractory Multiple Myeloma, Plasma Cell Leukemia
Treatment CAR-T (CAR-GPRC5D)
Clinical Study IdentifierNCT05219721
SponsorChunrui Li
Last Modified on5 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Subjects must satisfy all the following criteria to be enrolled in the study
age 18 to 75 years old, male or female
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
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)
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
ECOG performance score 0-2
Estimated life expectancy ≥ 12 weeks
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%
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
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
Subjects who are known to have GVHD or need long-term immunosuppressive therapy
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
days before leukapheresis
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
Subjects with hypertension that cannot be controlled by medication
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
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
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
Subjects with a history of organ transplantation
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)
Subjects participated in another interventional clinical study 1 months before signing the informed consent (ICF)
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)
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
Pregnant or lactating women
Subjects with mental illness or consciousness disorder or disease of the central nervous system
Other conditions that researchers consider inappropriate for inclusion
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