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This study is a single-arm, open-lable, phase I/II study to evaluate the efficacy and safety of GC012F in subjects with relapsed/refractory multiple myeloma.
Full description
Eligible subjects will be performed a leukapheresis procedure to manufacture GC012F. Subjects will receive a single dose of GC012F infusion at specified dose levels, after three consecutive days of lymphodepletion consisting of fludarabine and cyclophosphamide. Bridging therapy is allowed between leukapheresis and lymphodepletion.
Enrollment
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Inclusion criteria
Patients must have a diagnosis of active multiple myeloma as defined by the updated IMWG (International Myeloma Working Group) criteria, and meet one or more of the following criteria:
Have received at least 3 prior lines of therapy for multiple myeloma. Note: According to IMWG guidelines, a single line of therapy includes a full course of monotherapy, combination therapy with multiple drugs, or sequential treatment with multiple regimens (e.g., the use of a 3-6 cycle regimen of bortezomib combined with dexamethasone, followed by stem cell transplantation, consolidation therapy, and lenalidomide maintenance therapy, is considered a single line of therapy). Unless the best response was documented as progressive disease (PD) or the subject was intolerant to the therapy.
Prior therapy should include proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 antibodies.
Evaluated by investigator based on IMWG standards, subjects have a confirmed (through testing at a central or local laboratory) PD during or within 12 months following the most recent anti-myeloma treatment.
Voluntarily signed a written informed consent form (ICF).
The signing of ICF complies with the requirements of GCP and relevant national laws and regulations.
Males or females, aged 18-75 years old (including the thresholds).
Subjects should be willing and able to comply with the study visit schedule and other protocol requirements.
ECOG (Eastern Cooperative Oncology Group) performance score 0-1.
Estimated life expectancy ≥ 3 months.
Adequate functional reserve of organs:
Female subjects with fertility must:
Male subjects must agree to use condoms during sexual contact with pregnant females or females with fertility for at least 1 year after GC012F infusion, even if a successful vasectomy has been performed.
Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis.
Exclusion criteria
Prior treatment with CAR-T products for any target.
Have any of the following concomitant treatment history:
Patients' corticosteroid maintenance doses are greater than physiological replacement doses (i.e., prednisone ≥ 7.5 mg/day or hydrocortisone ≥ 12 mg/m^2/day).
Patients with any of the following heart diseases:
Patients requiring assisted oxygenation or mechanical ventilation or with oxygen saturation <95% on room air (patients with oxygen saturation <95%, but with lung function test results showing carbon monoxide diffusing capacity and forced expiratory volume in 1 second > 45% of predicted value, may be enrolled).
Patients with hypertension that is uncontrolled by drug therapy.
Patients with clinically significant bleeding symptoms or definite bleeding tendencies (e.g., gastrointestinal bleeding, bleeding gastric ulcers, etc.), hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophilia, coagulation disorders, hypersplenism, etc.) within 90 days prior to screening; have experienced arteriovenous thrombotic events (e.g., cerebrovascular diseases (including cerebral hemorrhage, cerebral infarction, etc.), deep vein thrombosis, and/or pulmonary embolism) within 180 days prior to screening.
Accompanied by other uncontrolled malignancies. The following are excluded: early-stage tumors that have received radical treatment (carcinoma in situ or grade 1 tumors, or non-ulcerated primary melanoma with a depth < 1 mm and no involvement of lymph nodes), basal cell skin cancer, squamous cell skin cancer, cervical carcinoma in situ, or breast carcinoma in situ that has received potential radical treatment.
Have received any of the following treatments:
Severe underlying medical conditions, such as:
Patients have CNS metastases or CNS involvement (including cranial neuropathies or mass lesions and leptomeningeal disease).
Positive results in any of the following tests:
Accompanied by plasma cell leukemia (peripheral blood plasma cells > 2.0×10^9/L), Waldenstrom macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy of undetermined significance, skin changes), or primary amyloidosis.
Patients have a history of severe hypersensitivity or allergy.
Contraindication or hypersensitivity to fludarabine, cyclophosphamide, and any component of experimental product.
Surgery plan within 2 weeks prior to leukapheresis or during the study (except for local anesthesia surgery, but not performed within 2 weeks after CAR-T infusion).
Pregnant or lactating, or planning to have a pregnancy during or within 1 year after treatment.
Acute toxicities (except for hematological toxicities and alopecia) caused by previous treatments have not recovered to ≤ grade 1.
Participated in other clinical trials within 4 weeks prior to ICF signing, or ICF signing date is within 5 half-lives of the drug from the last medication in the last drug clinical trial (whichever is longer).
Any situation in which investigators believe that participation in this study is not in the subject's best interests, or any situation that may hinder patients' participation in the entire trial or confuse the assessment.
Primary purpose
Allocation
Interventional model
Masking
110 participants in 1 patient group
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Central trial contact
Juan Du, MD; He Huang, MD
Data sourced from clinicaltrials.gov
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