A Phase I/II Study of the Safety, Tolerability and Efficacy of Belantamab Mafodotin (GSK2857916) in Combination With Iberdomide (CC-220)/Dexamethasone Versus Belantamab Mafodotin (GSK2857916)/Dexamethasone in Relapsed Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 88
- 试验地点
- 122
- 主要终点
- Progression-free survival (PFS) (Phase II)
研究概览
简要总结
This phase I/II trial tests the safety, side effects, best dose, and effectiveness of iberdomide in combination with belantamab mafodotin and dexamethasone in treating patients with multiple myeloma (MM) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Multiple myeloma is a cancer that affects white blood cells called plasma cells, which are made in the bone marrow and are part of the immune system. Multiple myeloma cells have a protein on their surface called B-cell maturation antigen (BCMA) that allows the cancer cells to survive and grow. Immunotherapy with iberdomide, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Belantamab mafodotin has been designed to attach to the BCMA protein, which may cause the myeloma cell to become damaged and die. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Iberdomide plus belantamab mafodotin may help slow or stop the growth of cancer in patients with multiple myeloma.
详细描述
PRIMARY OBJECTIVES:
I. To determine maximum tolerated dose (MTD) of iberdomide (CC-220) in combination with belantamab mafodotin and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). (PHASE I) II. To determine whether the combination of belantamab mafodotin/ iberdomide/dexamethasone improves progression-free survival (PFS) relative to belantamab mafodotin/dexamethasone in patients with RRMM. (PHASE II)
SECONDARY OBJECTIVES:
I. To summarize the incidence and cause for treatment delays, modifications and omissions. (PHASE I) II. To assess treatment response. (PHASE I) III. To obtain an estimate of the progression-free survival (PFS) and overall survival (OS) distribution. (PHASE I) IV. To determine minimal residual disease (MRD) negativity. (PHASE I) V. To observe and record anti-tumor activity. (PHASE I) VI. To determine whether the combination of belantamab mafodotin/ iberdomide/dexamethasone improves overall survival (OS) compared to belantamab mafadotin/dexamethasone in patients with RRMM. (PHASE II) VII. To evaluate the safety profile. (PHASE II) VIII. To estimate the ORR (per International Myeloma Working Group [IMWG] criteria), duration of response (DoR), and time to relapse (TTR). (PHASE II) XI. To determine MRD status. (PHASE II)
EXPLORATORY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •No evidence of active mucosal or internal bleeding.
- •No known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to belamaf or drugs chemically related to belamaf, or any of the components of the study treatment.
- •Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening.
- •Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment. Participant must not have current corneal epithelial disease except mild changes in corneal epithelium. For belantamab mafodotin, concomitant administration with strong inhibitors of OATP should be avoided.
- •RE-REGISTRATION ELIGIBILITY CRITERIA: Patients must meet criteria for progression of myeloma as defined by IMWG criteria indicated as any of the following:
- •≥ 25% increase in M-protein (must be at least 0.5 g/dl above nadir from last treatment regimen).
- •25% difference between involved and uninvolved serum free light chains from its nadir or
- •The development of new plasmacytomas or hypercalcemia not due to other causes. In the absence of progression by serum M protein or free light chain, biopsy of new plasmacytoma of extramedullary disease is warranted.
- •If refractory myeloma, it should be defined by IMWG criteria as disease which has become non-responsive or progressive on belamaf/dexamethasone.
- •RE-REGISTRATION ELIGIBILITY CRITERIA: Measurable disease defined by IMWG criteria as:
- •Serum M-protein ≥ 0.5 g/dL.
- •Urine monoclonal protein ≥ 200 mg/24h.
- •Serum FLC assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/l) and serum free light chain ratio is abnormal.
- •PET/CT or MRI findings consistent with (c/w) disease progression.
- •RE-REGISTRATION ELIGIBILITY CRITERIA: Absolute neutrophil count (ANC) ≥ 1,000/mm^
- •RE-REGISTRATION ELIGIBILITY CRITERIA: Platelet Count ≥ 75,000/mm^3 (or ≥ 50,000/mm^3 if BM plasma cells > 50%).
- •RE-REGISTRATION ELIGIBILITY CRITERIA: Calc. creatinine clearance ≥ 30 mL/min using Cockcroft-Gault equation.
- •RE-REGISTRATION ELIGIBILITY CRITERIA: Total bilirubin ≤ 2 mg/dL.
- •RE-REGISTRATION ELIGIBILITY CRITERIA: AST/ALT ≤ 2.5 x upper limit of normal (ULN).
- •RE-REGISTRATION ELIGIBILITY CRITERIA: Alkaline phosphatase ≤ 3 x ULN.
排除标准
- 未提供
研究组 & 干预措施
Phase II, Arm II (iberdomide, belantamab mafodotin)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Computed Tomography (Procedure)
Phase II, Arm I (belantamab mafodotin, dexamethasone)
Patients receive belantamab mafodotin IV on day 1 and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients who progress may cross over to Arm II. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Bone Marrow Aspiration (Procedure)
Phase II, Arm I (belantamab mafodotin, dexamethasone)
Patients receive belantamab mafodotin IV on day 1 and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients who progress may cross over to Arm II. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Belantamab Mafodotin (Biological)
Phase II, Arm II (iberdomide, belantamab mafodotin)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Phase II, Arm I (belantamab mafodotin, dexamethasone)
Patients receive belantamab mafodotin IV on day 1 and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients who progress may cross over to Arm II. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Bone Marrow Biopsy (Procedure)
Phase II, Arm II (iberdomide, belantamab mafodotin)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Bone Marrow Biopsy (Procedure)
Phase II, Arm II (iberdomide, belantamab mafodotin)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Iberdomide (Drug)
Phase I (iberdomide, belantamab mafodotin, dexamethasone)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Echocardiography (Procedure)
Phase I (iberdomide, belantamab mafodotin, dexamethasone)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Phase I (iberdomide, belantamab mafodotin, dexamethasone)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Computed Tomography (Procedure)
Phase I (iberdomide, belantamab mafodotin, dexamethasone)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Positron Emission Tomography (Procedure)
Phase I (iberdomide, belantamab mafodotin, dexamethasone)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Bone Marrow Biopsy (Procedure)
Phase I (iberdomide, belantamab mafodotin, dexamethasone)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Bone Marrow Aspiration (Procedure)
Phase I (iberdomide, belantamab mafodotin, dexamethasone)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Biospecimen Collection (Procedure)
Phase II, Arm I (belantamab mafodotin, dexamethasone)
Patients receive belantamab mafodotin IV on day 1 and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients who progress may cross over to Arm II. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Echocardiography (Procedure)
Phase II, Arm I (belantamab mafodotin, dexamethasone)
Patients receive belantamab mafodotin IV on day 1 and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients who progress may cross over to Arm II. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Computed Tomography (Procedure)
Phase II, Arm I (belantamab mafodotin, dexamethasone)
Patients receive belantamab mafodotin IV on day 1 and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients who progress may cross over to Arm II. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Phase II, Arm I (belantamab mafodotin, dexamethasone)
Patients receive belantamab mafodotin IV on day 1 and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients who progress may cross over to Arm II. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Positron Emission Tomography (Procedure)
Phase II, Arm II (iberdomide, belantamab mafodotin)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Echocardiography (Procedure)
Phase II, Arm I (belantamab mafodotin, dexamethasone)
Patients receive belantamab mafodotin IV on day 1 and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients who progress may cross over to Arm II. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Biospecimen Collection (Procedure)
Phase II, Arm II (iberdomide, belantamab mafodotin)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Bone Marrow Aspiration (Procedure)
Phase II, Arm II (iberdomide, belantamab mafodotin)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Biospecimen Collection (Procedure)
Phase II, Arm II (iberdomide, belantamab mafodotin)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Positron Emission Tomography (Procedure)
Phase II, Arm II (iberdomide, belantamab mafodotin)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Dexamethasone (Drug)
Phase II, Arm II (iberdomide, belantamab mafodotin)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Belantamab Mafodotin (Biological)
Phase II, Arm I (belantamab mafodotin, dexamethasone)
Patients receive belantamab mafodotin IV on day 1 and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients who progress may cross over to Arm II. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Dexamethasone (Drug)
Phase I (iberdomide, belantamab mafodotin, dexamethasone)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Belantamab Mafodotin (Biological)
Phase I (iberdomide, belantamab mafodotin, dexamethasone)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Dexamethasone (Drug)
Phase I (iberdomide, belantamab mafodotin, dexamethasone)
Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.
干预措施: Iberdomide (Drug)
结局指标
主要结局
Progression-free survival (PFS) (Phase II)
时间窗: From randomization to the time of documented disease progression and/or death due to any cause, assessed up to 3 years
Will be compared between the two treatment arms. the methods of Kaplan and Meier will be used to graphically evaluate these distributions as well as to estimate the median PFS and corresponding 95% confidence intervals.
Maximum tolerated dose (MTD) of iberdomide (Phase I)
时间窗: During the first cycle of therapy, up to 28 days
MTD will be defined as the highest dose level among those tested where at most one out of 6 patients develops a DLT prior to the start of their second cycle of treatment. Will be assessed by NCI CTCAE v 5.0.
次要结局
- Rate of grade 3+ Adverse Events (AEs)(Up to 3 years)
- Overall Survival (OS)(Up to 3 years.)
- Complete response (CR) rate(up to 3 years)
- Overall response rate (ORR)(up to 3 years)
- Duration of response (DoR)(p to 3 years)