Belantamab Mafodotin, Cyclophosphamide and Dexamethasone in Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events in Dose Escalation
研究概览
简要总结
Evaluate the efficacy and safety of Belantamab Mafodotin, cyclophosphamide, and dexamethasone in patients with Relapsed/Refractory Multiple Myeloma
详细描述
This is a Phase I/II, open-label study to evaluate the efficacy and safety of Belantamab Mafodotin, cyclophosphamide, and dexamethasone.
In Phase I, the subjects will be assigned into two arms and there are two dose levels for Belantamab Mafodotin and there are two dose levels of cyclophosphamide in each arm.
In Phase II, once tolerability of the highest planned dose is established, the patients will be assessed for response rate. The arm with acceptable toxicity and best response will be further assessed in the expansion cohort.
Belantamab mafodotin was approved by the U.S. Food and Drug Administration (FDA) on Aug 5, 2020, for treating patients with relapsed/refractory multiple myeloma. Cyclophosphamide and dexamethasone are both approved by the FDA. But the combinations with these three drugs to treat people with relapsed/refractory multiple myeloma has not been approved by the FDA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologically confirmed diagnosis of Refractory MM; failed at least 3 prior lines of anti-myeloma treatments, including an anti-CD38 antibody (e.g., daratumumab) alone or in combination, and is refractory to an IMiD (i.e., lenalidomide or pomalidomide), and to a proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib). (Refractory myeloma is defined as disease that is nonresponsive while on primary or salvage therapy or progresses within 60 days of last therapy. Nonresponsive disease is defined as either failure to achieve at least minimal response or development of progressive disease (PD) while on therapy).
- •Has measurable disease with at least one of the following:
- •Serum M-protein ≥0.5 g/dL (≥ 5 g/L)
- •Urine M-protein ≥ 200 mg/24h
- •Serum FLC assay: Involved FLC level ≥10 mg/dL and an abnormal ratio (<0.26 or >1.65)
- •Provide signed written informed consent.
- •18 years or older (at the time consent is obtained).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Participants with a history of autologous stem cell transplant or Prior BCMA targeted therapy (e.g. CAR-T cells, BiTes) can enroll on the study provided that:
- •Therapy was >100 days prior to study enrolment.
- •No active infection(s).
- •Adequate organ system function (as defined by inclusion criteria #7).
- •Female and Male patients: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Prior treatment-related toxicities must be ≤ Grade 1 except peripheral neuropathy (Grade-2).
排除标准
- •Systemic anti-myeloma therapy within ≤14 days or 5 half-lives, whichever is shorter, or plasmapheresis within 7 days prior to treatment.
- •Systemic treatment with high dose steroids (equivalent to ≥ 60 mg prednisone daily for ≥4 days) within the past 14 days.
- •Symptomatic amyloidosis, active CNS disease, active plasma cell leukemia at the time of screening.
- •Prior allogeneic stem cell transplant (SCT). NOTE - Participants who have undergone syngeneic transplant may be allowed if no history of GvHD.
- •Current corneal epithelial disease except mild punctate keratopathy.
- •Evidence of active bleeding.
- •Any major surgery within the last four weeks.
- •Presence of active renal condition (infection, dialysis); isolated proteinuria from MM is allowed provided participants fulfil the adequate organ system function criteria (as defined by inclusion criteria #7).
- •Any serious and/or unstable pre-existing medical, psychiatric disorder or lab abnormalities that affect patients' safety, obtaining informed consent or compliance with study procedures.
- •Current unstable liver disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
- •Other malignancies except for malignancy from which the patients have been disease-free > 2 years.
- •Evidence of cardiovascular disease including any of the following:
- •Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including second degree (Mobitz Type II) or third degree atrioventricular (AV) block.
- •History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening.
- •Class III or IV heart failure as defined by the New York Heart Association functional classification system.
- •Uncontrolled hypertension.
- •Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, daratumumab, bortezomib, boron or mannitol or any other components of the study treatment.
- •Active infection requiring treatment.
- •Known HIV infection.
- •Presence of hepatitis B surface antigen (HbsAg), or hepatitis B core antibody (HbcAb), at screening or within 3 months prior to first dose of study treatment. Note: presence of Hep B surface antibody (HBsAb) indicating previous vaccination will not exclude a participant.
- •Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
- •NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Hepatitis RNA testing is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.
- •Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening.
- •Pregnant or lactating female.
- •Concomitant administration of strong P-glycoprotein inhibitors and inhibitors of OATP will be avoided.
研究组 & 干预措施
Arm A
- Dose level 1: The subject will take 1.9 mg/kg of Belantamab Mafodotin, 300 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 of each 3 weeks cycles.
- Dose level 2: The subject will take 1.9 mg/kg of Belantamab Mafodotin, 500 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 each 3 weeks cycles.
干预措施: Belantamab Mafodotin, Cyclophosphamide and Dexamethasone (Drug)
Arm B
- Dose level 1: The subject will take 2.5 mg/kg of Belantamab Mafodotin, 300 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 of each 6 weeks cycles.
- Dose level 2: The subject will take 2.5 mg/kg of Belantamab Mafodotin, 500 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 each 6 weeks cycles.
干预措施: Belantamab Mafodotin, Cyclophosphamide and Dexamethasone (Drug)
结局指标
主要结局
Number of Participants With Adverse Events in Dose Escalation
时间窗: Up to 6 weeks
Overall incidence and severity of Adverse Events in Number of Participants with Adverse Events in Dose Escalation
Response Rate in Dose Escalation and Expansion Cohort
时间窗: Up to 12 weeks
Number of Participants With response rate in Dose Escalation and Expansion Cohort. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
次要结局
- Number of Participants With Disease Progression(From date of randomization until the date of death from any cause, assessed up to 3 years)
- Number of Participants According to Best Response(From date of randomization until the date of death from any cause, assessed up to 3 years)
- Overall Survival(From date of randomization until the date of death from any cause, assessed up to 3 years)
研究者
Ashraf Badros
Director of Multiple Myeloma Service
University of Maryland, Baltimore