Multiple myeloma
Conditions
Interventions
Experimental group:Equecabtagene Autoleucel Injection
Control group:DPd(Daratumumab, Pomalidomide, Dexamethasone) or PVd (Pomalidomide, Bortezomib, Dexamethasone)
Sponsors
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1) 18 to 75 years (inclusive of critical values), either gender; 2) 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 [see Appendix 3]); Documented disease progression during or within 12 months after the most recent anti-myeloma therapy; • Subjects who have only received one line therapy: if autologous stem cell transplantation (ASCT) has been performed, disease progression should occur within 24 months after ASCT, or the subject is judged by the investigator to be unsuitable for a second ASCT; if prior ASCT has not been performed, patients should be judged by the investigator not suitable for ASCT. 3) Subjects was lenalidomide-refractory during prior therapy: subjects did not achieve minimal response (MR) or better during any prior treatment regimen containing lenalidomide, or experienced disease progression on or within 60 days after the last dose of lenalidomide (including lenalidomide maintenance therapy). 4) Measurable disease at screening was defined by either of the following criteria: • Serum monoclonal protein (M-protein) level: >=5 g/L; • Urine M protein level >= 200 mg/24 hours; • Serum free light chain >=100 mg/L and abnormal serum kappa/lambda free light chain ratio; 5) ECOG score of 0 or 1; 6) Subjects must have appropriate organ function and meet all of the following laboratory test results before enrollment: • Haematology: absolute neutrophil count (ANC) >= 1×10^9/L (support with growth factor is allowed, but must not have received support treatment 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); haemoglobin >= 60 g/L (must not have received red blood cells [RBC] transfusion within 7 days prior to laboratory test); • Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 40 ml/min; • Coagulation: fibrinogen>=1.0 g/L; activated partial thromboplastin time (APTT) 91%; • Left ventricular ejection fraction (LVEF)>=50%; 7) Subjects agree to take effective tools or drug contraceptive measures (excluding safe period contraception) after signing the informed consent form, and take effective contraceptive measures one year after CAR-T cell infusion if assigned to the CAR-T group, or 6 months after the last dose if assigned to the control group; 8) Subjects must agree to sign or personally sign an ethics committee-approved informed consent form before starting any screening procedures.
Exclusion criteria
Exclusion criteria: 1) 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; 2) Prior treatment of any CAR-T therapy; 3) Prior exposure to any BCMA-targeted therapy; 4) 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); 5) Subjects received the following anti-tumor treatments before enrollment: • Treated with an immunomodulator within 7 days, or; • 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; • Treatment with monoclonal antibody for multiple myeloma within 21 days, or; • Received other anti-cancer therapy within 14 days or at least 5 half-lives (whichever is shorter) prior to enrollment. 6) Significant cardiac disorder: including but not limited to unstable angina pectoris, myocardial infarct (within 6 months prior to screening), congestive cardiac failure (New York Heart Association [NYHA] class>=III), severe arrhythmia; 7) Unstable systemic disease as judged by the investigator: including but not limited to severe liver, renal, or metabolic disease requiring medication; 8) The subject will not be able to participate in this study if the investigator determines that the subject meets any of the following conditions: • Subjects with a history of allergic reaction to the excipient components (DMSO and albumin) of Eque-cel, fludarabine, cyclophosphamide, tocilizumab, or; • Subjects who are intolerant to dexamethasone, or; • 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 9) Subjects will not be eligible for treatment with the PVd regimen but may receive treatment with the DPd regimen if the following conditions are met according to the investigator's judgment: • Not meeting the re-treatment criteria of bortezomib (not achieving PR or above after prior bortezomib treatment, or having confirmed disease progression according to IMWG criteria during or within 6 months after prior bortezomib treatment); or; • Subjects with life-threatening allergy, hypersensitivity or intolerance (intolerance is defined as discontinuation of previous treatment due to any AE related to bortezomib) to bortezomib and its excipients; • Grade 2 peripheral neuropathy with pain or Grade 3 or higher peripheral neuropathy as defined by NCI-CTCAE v5.0; 10) Subjects will not be eligible for treatment with the DPd regimen but may receive treatment with the PVd regimen if the following conditions are met according to the investigator's judgment: • Subjects with life-threatening allergy, hypersensitivity, or intolerance (intolerance is defined as discontinuation of previous treatment due to any AE related to daratumumab) to daratumumab and its excipients; or • Subjects with previous or current diagnosis of chronic obstructive lung disease (COPD) or suspected to have COPD, with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal by pulmonary function test; 11) Have ma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival, PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall MRD negativity rate;Duration of MRD negativity;Complete Response rate;Rate of very good partial response or better ;Overall Response Rate;Event Free Survival;Overall Survival;Time to Next Treatment;Safety Endpoint;Pharmacokinetic Endpoint;Pharmacodynamic Endpoint;Health Related Quality of Life Endpoint;Minimal Residual Disease negativity rate at 12 months;Duration of Response; | — |
Countries
China
Contacts
Public ContactLugui Qiu
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed