A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)

Korábbi kezelés

• Subjects who have used or required long-term immune-suppressive agents (e.g., cyclosporine or systemic steroids) within 14 days prior to enrollment, but the use of physiological substitutes, intermittent, topical, and inhaled steroids is allowed.
• Subjects who have undergone autologous haematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks prior to randomization, or who have previously undergone allogeneic haematopoietic stem cell transplantation (Allo-HSCT).
• Subjects received the following anti-tumor treatments before enrollment: (1)Treated with an immunomodulator within 7 days, or; (2)Received plasma exchange, radiotherapy (except local radiotherapy for myeloma-related bone lesions), cytotoxic chemotherapy, treatment with proteasome inhibitors or other investigational drug within 14 days, or; (3) Treatment with monoclonal antibody for multiple myeloma within 21 days, or; (4) Received other anti-cancer therapy within 14 days or at least 5 half-lives (whichever is shorter) prior to enrollment.
• Subjects with concurrent plasma cell leukemia(defined as plasma cell proportion in peripheral blood > 5%), Waldenström macroglobulinaemia, POEMS syndrome (polyneuropathy, organ hypertrophy, endocrinopathy, monoclonal protein and skin changes) or primary amyloidosis during screening period.
• Patients with concomitant non-paraskeletal extramedullary soft tissue plasmacytoma (EM-E); patients with multiple paraskeletal extramedullary lesions (EM-B) where the longest diameter of the extramedullary part of any lesion is >3 cm; patients with a single paraskeletal extramedullary lesion (EMB) where the longest diameter of the extramedullary part is >5 cm;.
• Had major surgery within 2 weeks prior to randomization or planned to have surgery within 2 weeks after study treatment (except for subjects who were scheduled to have surgery under local anesthesia).
• The subject has a history of central nervous system disorder within 6 months prior to signing the informed consent form.
• Non-hematological toxicity reactions due to prior treatment have not resolved to baseline or ≤ Grade 1 (NCI-CTCAE v5.0, alopecia, Grade 2 peripheral neuropathy were excepted).

Más betegség

• Significant cardiac disorder.
• Unstable systemic disease as judged by the investigator: including but not limited to severe liver, renal, or metabolic disease requiring medication.
• Have malignancies other than multiple myeloma within 5 years before screening, excluding cervical carcinoma in situ after radical surgery, basal cell or squamous cell skin cancer, localized cancer of prostate after radical prostatectomy, breast ductal carcinoma in situ after radical mastectomy or carcinoma papillary thyroid after radical thyroidectomy.
• Subject with uncontrollable infection.
• Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and hepatitis B virus (HBV) DNA quantification in peripheral blood was higher than the lower limit of detection; hepatitis C virus (HCV) antibody positive and hepatitis C virus (HCV) RNA positive in peripheral blood; Human immunodeficiency virus (HIV) antibody positive; Syphilis test positive; positive cytomegalovirus (CMV) DNA.
• Subjects had other conditions that the investigator considered unsuitable for enrollment.

Laborértékek

• The subject will not be able to participate in this study if the investigator determines that the subject meets any of the following conditions: (1) Subjects with a history of allergic reaction to the excipient components (DMSO and albumin) of Eque-cel, fludarabine, cyclophosphamide, tocilizumab, or; (2) Subjects who are intolerant to dexamethasone, or; (3) Subjects who have a Life-threatening allergy, hypersensitivity reaction, or intolerance to pomalidomide and/or its excipients (intolerance is defined as discontinuation of prior treatment due to any AE related to pomalidomide) or;

Egyéb

• Subjects suspected or confirmed to have central nervous system involvement of MM during the screening period.
• Pregnant or breastfeeding women.

• 18 to 75 years of age (inclusive of critical values), either gender.
• The subject was previously diagnosed with multiple myeloma and had received 1-2 lines of therapy (including chemotherapy regimens based on proteasome inhibitors and immunomodulatory agents, with each line of therapy receiving at least 1 full cycle ; Documented disease progression during or within 12 months after the most recent anti-myeloma therapy.
• Subjects was lenalidomide-refractory during prior therapy.
• ECOG score of 0 or 1.
• Subjects must have appropriate organ function and meet all of the following laboratory test results before enrollment:
  • (1) Haematology: Absolute neutrophil count (ANC) ≥1×10\^9/L (prior use of granulocyte colony-stimulating factor [G-CSF] support is permitted, but no supportive therapy have been received within 7 days before the laboratory test);Absolute lymphocyte count (ALC) ≥0.3×10\^9/L; Platelets ≥50×10\^9/L (must not have received platelet transfusion within 7 days prior to laboratory test); Hemoglobin ≥60g/L (must not have received red blood cells transfusion within 7 days prior to laboratory test); (2) Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times of upper limit of normal (ULN); Serum total bilirubin ≤1.5 times of ULN; (3) Renal function: creatinine clearance (CrCl) calculated by Cockcroft-Gault formula ≥ 40 ml/min; (4) Coagulation: fibrinogen≥1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, pro-thrombin time (PT) ≤ 1.5 × ULN; (5) Pulse oxygen saturation > 91%; (6) Left ventricular ejection fraction (LVEF)≥50%;
• Subjects agree to use effective tools or drug contraception (excluding safe period contraception) after signing the informed consent form.
• Subjects must agree to sign or personally sign an ethics committee-approved informed consent form before starting any screening procedures.