Multiple Myeloma Clinical Trial
— FUMANBA-03Official title:
A Phase III Randomized, Controlled Study of Equecabtagene Autoleucel Injection in Subjects With Lenalidomide-Refractory R/R Multiple Myeloma
This is a multicenter, randomized, controlled, open-label, phase III clinical study to evaluate the efficacy of Equecabtagene Autoleucel Injection versus standard therapy in subjects with lenalidomid-refractory RRMM who have received 1-2 lines of prior therapy.
Status | Recruiting |
Enrollment | 240 |
Est. completion date | December 2030 |
Est. primary completion date | August 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria: 1.18 to 70 years of age (inclusive of cutoff), regardless of gender. 2. Subjects were previously diagnosed with multiple myeloma and received 1-2 lines of proteasome inhibitor and immunomodulatory-based chemotherapy, with at least one complete cycle of each line of treatment; Documented disease progression during or within 12 months after the most recent anti-myeloma therapy. 3. Subjects were previously refractory to lenalidomide treatment. 4.ECOG score of 0 or 1. 5. Subjects must have adequate organ function and meet all the following laboratory test results before enrollment: ? Blood routine: absolute neutrophil count (ANC) =1×10^9/L (growth factor support allowed, but no supportive treatment within 7 days before laboratory test); Absolute lymphocyte count (ALC) =0.3×10^9/L; Platelet count =50×10^9 / L (no supportive platelets infusion allowed within 7 days before lab test ); Hemoglobin =60g/L (no transfusion of red blood cells [RBC] within 7 days before the laboratory test; the use of recombinant human erythropoietin was allowed); (2) liver 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 according to Cockcroft - Gault formula of creatinine clearance (CrCl) should be =40 ml/min; ? Coagulation function: fibrinogen =1.0g/L; aPTT=1.5 x ULN, prothrombin time (PT)=1.5 x ULN; ? oxygen saturation>91%; ? Left ventricular ejection fraction (LVEF) =50%. 6. Subjects agree to use effective tools or drug contraception (excluding safe period contraception) after signing the informed consent form. 7. Before starting any screening program, subjects must have to agreed to sign or sign the informed consent in person which have been approved by the ethics committee. Exclusion Criteria: 1. Subjects who have used or need long-term use of immunosuppressive agents, such as cyclosporine or systemic steroid) 14days before enrollment; but the use of physiological substitute, intermittent, local and inhaled steroids is allowed. 2. Patients who had undergone autologous hematopoietic stem-cell transplantation (Auto-HSCT) within 12 weeks before randomization or prior allogeneic hematopoietic stem-cell transplantation (Allo-HSCT); 3. The subject received the following anti-tumor therapy before enrollment: ? immunomodulatory therapy within 7 days, or; ? Plasma exchange, radiotherapy (except for local radiotherapy for myeloma-associated bone lesions), cytotoxic chemotherapy, proteasome inhibitor, or other investigation drug in clinical trial within 14 days; or (3) monoclonal antibody treatment for multiple myeloma within 21 days, or; (4) within 14 days or at least five half-life (will be subject to a shorter time) of other anti-tumor treatment except for the above-mentioned ones; 4. Severe heart disease; 5. Unstable Systemic diseases per investigator's evaluation: including, but not limited to, severe hepatic, renal, or metabolic diseases requiring medical treatment; 6. subjects with the following conditions per investigator's evaluation will not be able to participate in the study: (1) allergic to excipients of Equecabtagene Autoleucel Injection (DMSO and albumin), fludarabine, cyclophosphamide, tocilizumab, or; ? subjects intolerant to dexamethasone, or; (3) subjects who have life-threatening allergy, allergic reactions, or intolerance (intolerance is defined as end of treatment for any pomalidomide related AE) with pomalidomide, or; ? subjects who met the NCI-CTCAE v5.0 definition of grade 2 peripheral neuropathy with pain or = grade 3 peripheral neuropathy; 7. Diagnosed with another malignancy within 5 years before screening except for multiple myeloma, excluding radical cervical carcinoma in situ, basal cell or squamous epithelial cell skin cancer, radical localized prostate cancer, radical ductal carcinoma in situ of the breast, or papillary thyroid cancer; 8. Patients with suspected or existed central nervous system involvement of plasma cell neoplasms during screening; 9. subjects with plasma cell leukemia (defined as > 5% peripheral plasma cells), Waldenstrom macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and cutaneous changes), or primary amyloidosis previously or during screening period; 10. Multiple myeloma patients with extramedullary lesions (except for a single parosteal extramedullary lesion =3cm in maximum transverse diameter) 11. Subject who underwent major surgery within 2 weeks before randomization or have surgery plan within 2 weeks after study treatment (except for those scheduled surgery under local anesthesia); 12. Subject with uncontrollable infection; 13. The hepatitis b surface antigen (HBsAg) or hepatitis b core antibody (HBcAb) positive with hepatitis b virus (HBV) DNA quantification higher than the detection limit; Hepatitis C virus (HCV) antibody positive with HCV RNA positive in peripheral blood; human immunodeficiency virus (HIV) antibody positive; Syphilis testing positive; 14. Women who are pregnant or lactating; 15. The subject has a existed central nervous system disease or with medical history of CNS disease; 16. Non-hematologic toxicity due to prior therapy havn't been resolved to baseline or = grade 1 (NCI-CTCAE version 5.0, excluding alopecia and grade 2 peripheral neuropathy) 17. The subject had other conditions unsuitable for enrollment per investigator's evaluation. |
Country | Name | City | State |
---|---|---|---|
China | Beijing Chao-Yang Hospital, Capital Medical University | Beijing | |
China | Peking Union Medical College Hospital | Beijing | |
China | Peking University First Hospital | Beijing | |
China | Peking University Third Hospital | Beijing | |
China | People's Hospital of Peking University | Beijing | |
China | The first hospital of Jilin University | Chang chun | |
China | West China School of Medicine, West China Hospital of Sichuan University | Chengdu | |
China | Xinqiao Hospital of AMU | Chongqing | |
China | Nanfang Hospital, Southern Medical University | Guangzhou | |
China | Sun Yat-sen University Cancer Centre | Guangzhou | |
China | Zhujiang Hospital of Southern Medical University Guangdong | Guangzhou | |
China | The First Affiliated Hospital, College of Medicine, Zhejiang University | Hangzhou | Zhejiang |
China | The Second Affiliated Hospital,Zhejiang University School of Medicine | Hangzhou | |
China | Qilu Hospital of Shangdong University | Jinan | |
China | The First Affiliated Hospital of Nanchang University | Nanchang | |
China | Affiliated Drum Tower Hospital, Medical School of Nanjing University | Nanjing | |
China | Jiangsu Province Hospital | Nanjing | |
China | The Affiliated People's Hospital of Ningbo University | Ningbo | |
China | Ruijin Hospital, Shanghai Jiaotong University School of Medicine | Shanghai | |
China | The First Affiliated Hospital of Soochow University | Suzhou | |
China | Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences | Tianjing | |
China | Tianjin Medical University General Hospital | Tianjing | |
China | The First Affiliated Hospital of Wenzhou Medical University | Wenzhou | |
China | Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology | Wuhan | |
China | Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology | Wuhan | |
China | Henan Cancer Hospital Affilated Cancer Hospital of Zhengzhou University | Zhengzhou |
Lead Sponsor | Collaborator |
---|---|
Nanjing IASO Biotechnology Co., Ltd. |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Progression Free Survival per independent review committee, PFS per IRC | The time from randomization to the first time of documented disease progression or death from any cause per IRC | up to 5 years from randomization | |
Secondary | Minimal Residual Disease Negativity Rate | Proportion of subjects with MRD-negative bone marrow detection by next-generation flow cytometry following study therapy | up to 5 years from randomization | |
Secondary | Duration of MRD negativity | The time from the first MRD negative to the first MRD negative positive transfer | up to 5 years from randomization | |
Secondary | Complete Response rate | Proportion of subjects who achieved CR or better response after receiving study therapy | up to 5 years from randomization | |
Secondary | Rate of very good partial response or better | Proportion of subjects who achieved strict complete response (sCR), CR, and VGPR after receiving study therapy | up to 5 years from randomization | |
Secondary | Overall Response Rate | Proportion of subjects who achieved sCR, CR, VGPR, and PR after receiving study therapy | up to 5 years from randomization | |
Secondary | Event Free Survival | The time from the start of randomization until the first occurrence of any of the following events, including death, disease progression, change of treatment, addition of another treatment, fatal or intolerable side effects | up to 5 years from randomization | |
Secondary | Overall Survival | The time from randomization until death from any cause | up to 5 years from randomization | |
Secondary | Time to Next Treatment | The time from receipt of the trial drug to initiation of the next line of treatment | up to 5 years from randomization | |
Secondary | incidence of Adverse events | Safety Endpoint | up to 5 years from randomization | |
Secondary | Pharmacokinetic Endpoint-Cmax | The maximum concentration (Cmax) of CAR VCN and BCMA CAR-T in peripheral blood after CAR-T infusion | up to 5 years from Eque-cel infusion | |
Secondary | Pharmacokinetic Endpoint-Tmax | the time for CAR VCN and BCMA CAR-T to reach the maximum concentration (Tmax) after CAR-T infusion | up to 5 years from Eque-cel infusion | |
Secondary | Pharmacokinetic Endpoint-AUC | Area under the curve of 29, 85, 169 days and the last time point of PK detection (AUC0-29d, AUC0-85d, AUC0-169d, AUC0-last) for CAR VCN; Area under the curve of 29 days (AUC0-29) for BCMA CAR-T. | up to 5 years from Eque-cel infusion | |
Secondary | Pharmacodynamic Endpoint | The concentration of soluble BCMA in peripheral blood of experimental group at each time point | up to 5 years from Eque-cel infusion | |
Secondary | Health Related Quality of Life Endpoint | Symptoms, function, and overall HRQoL were collected using the validated Patient-Reported Outcomes (PRO) questionnaire | up to 5 years from randomization |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05027594 -
Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT02412878 -
Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma
|
Phase 3 | |
Completed |
NCT01947140 -
Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
|
Phase 1/Phase 2 | |
Recruiting |
NCT05971056 -
Providing Cancer Care Closer to Home for Patients With Multiple Myeloma
|
N/A | |
Recruiting |
NCT05243797 -
Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation
|
Phase 3 | |
Active, not recruiting |
NCT04555551 -
MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma
|
Phase 1 | |
Recruiting |
NCT05618041 -
The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies
|
N/A | |
Active, not recruiting |
NCT03844048 -
An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
|
Phase 3 | |
Recruiting |
NCT03412877 -
Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer
|
Phase 2 | |
Completed |
NCT02916979 -
Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG
|
Phase 1 | |
Recruiting |
NCT03570983 -
A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion
|
Phase 2 | |
Terminated |
NCT03399448 -
NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells)
|
Phase 1 | |
Completed |
NCT03665155 -
First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody
|
Phase 1/Phase 2 | |
Completed |
NCT02812706 -
Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT05024045 -
Study of Oral LOXO-338 in Patients With Advanced Blood Cancers
|
Phase 1 | |
Active, not recruiting |
NCT03989414 -
A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM)
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT03792763 -
Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients
|
Phase 2 | |
Withdrawn |
NCT03608501 -
A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation
|
Phase 2 | |
Recruiting |
NCT04537442 -
Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT02546167 -
CART-BCMA Cells for Multiple Myeloma
|
Phase 1 |