A Phase 2 Study of Cusatuzumab Plus Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 103
- 试验地点
- 56
- 主要终点
- Percentage of Participants With Complete Remission (CR)
研究概览
简要总结
The purpose of this study is to determine the efficacy of cusatuzumab in combination with azacitidine in participants with previously untreated acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy.
详细描述
AML is a heterogeneous disease characterized by uncontrolled clonal expansion of hematopoietic progenitor cells. As the most common form of acute leukemia, AML accounts for the largest number of annual deaths from leukemia. Over 95 percent (%) of AML blasts harvested from newly diagnosed AML participants expressed Cluster of Differentiation (CD) 70 on the cell surface. Cusatuzumab (JNJ-74494550) is a humanized monoclonal antibody of camelid origin, binding with tight affinity to human CD70. Cusatuzumab has been modified to induce enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) for therapeutic use in participants with cancer. Azacitidine is a pyrimidine nucleoside analogue of cytidine with antineoplastic activity and is indicated for the treatment of adult participants with AML or intermediate 2 and high-risk myelodysplastic syndrome (MDS) with greater than 20% marrow blasts who are not eligible for hematopoietic stem cell transplantation. This study will evaluate 2 doses of cusatuzumab in combination with standard dose azacitidine in participants with AML who are not candidates for intensive chemotherapy (Part 1). Part 1 data will be reviewed by a Data Review Committee to select a preferred dose of cusatuzumab. The study will include a Screening Phase (28 days prior to randomization), a Treatment Phase, and a Follow-up Phase. The study includes evaluations like vital signs, electrocardiogram, spirometry test, serum chemistry and hematology tests.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Acute myeloid leukemia (AML) according to World Health Organisation (WHO) 2016 criteria and fulfilling all of the following criteria that defines those who are "not candidates for intensive chemotherapy":
- •greater than or equal to (>=)75 years of age or
- •less than (<) 75 years of age with at least one of the following comorbidities: Eastern Cooperative Oncology Group (ECOG) Performance Status of 2; Severe cardiac comorbidity defined as congestive heart failure or ejection fraction less than or equal to (<=) 50 percent (%); Severe pulmonary comorbidity defined as documented pulmonary disease with lung diffusing capacity for carbon monoxide (DLCO) <=65% of expected, or forced expiratory volume in 1 second (FEV1) <=65% of expected or dyspnea at rest requiring oxygen; Moderate hepatic impairment defined according to NCI organ dysfunction classification criteria (total bilirubin >=1.5 up to 3 times upper limit of normal [ULN]); Creatinine clearance <45 milliliter per minute per 1.73 meter square (mL/ min/1.73 m^2); Comorbidity that, in the Investigator's opinion, makes the participant unsuitable for intensive chemotherapy and must be documented and approved by the Sponsor before randomization
- •De novo or secondary AML
- •Previously untreated AML (except: emergency leukapheresis, hydroxyurea, and/or 1 dose of cytarabine [example: 1-2 gram per meter square {g/m^2}] during the Screening Phase to control hyperleukocytosis. These treatments must be discontinued >=24 hours prior to start of study drug). Empiric all trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia (APL) is permitted but APL must be ruled out and ATRA must be discontinued >=24 hours prior to the start of study drug
- •Not eligible for an allogeneic hematopoietic stem cell transplantation
- •ECOG Performance Status score of 0, 1 or 2
排除标准
- •Acute promyelocytic leukemia
- •Leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system
- •Use of immune suppressive agents for the past 4 weeks before the first administration of cusatuzumab on Cycle 1 Day
- •For regular use of systemic corticosteroids, participants may only be included if free of systemic corticosteroids for a minimum of 5 days before the first administration of cusatuzumab. Treatment of adrenal insufficiency with physiologic replacement doses of corticosteroids are allowed
- •Prior treatment with a hypomethylating agent for treatment of AML or myelodysplastic syndrome (MDS)
- •Active malignancies (that is, progressing or requiring treatment in the last 24 months) other than the disease being treated under the study
- •Any active systemic infection
- •Known allergies, hypersensitivity, or intolerance to cusatuzumab or azacitidine or its excipients (that is, mannitol, an excipient of azacitidine)
研究组 & 干预措施
Azacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kg
Participants will receive azacitidine 75 milligram per meter square (mg/m^2) subcutaneously (SC) or intravenously (IV) on Day 1 through Day 7 and cusatuzumab 10 milligram per kilogram (mg/kg) IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a data review committee.
干预措施: Azacitidine (Drug)
Azacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kg
Participants will receive azacitidine 75 milligram per meter square (mg/m^2) subcutaneously (SC) or intravenously (IV) on Day 1 through Day 7 and cusatuzumab 10 milligram per kilogram (mg/kg) IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a data review committee.
干预措施: Cusatuzumab (Drug)
Azacitidine 75 mg/m^2 and Cusatuzumab 20 mg/kg
Participants will receive azacitidine 75 mg/m^2 SC or IV on Day 1 through Day 7 and cusatuzumab 20 mg/kg IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a data review committee.
干预措施: Azacitidine (Drug)
Azacitidine 75 mg/m^2 and Cusatuzumab 20 mg/kg
Participants will receive azacitidine 75 mg/m^2 SC or IV on Day 1 through Day 7 and cusatuzumab 20 mg/kg IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a data review committee.
干预措施: Cusatuzumab (Drug)
结局指标
主要结局
Percentage of Participants With Complete Remission (CR)
时间窗: Up to 3 years and 5 months
Complete remission based on European Leukemia Network (ELN) 2017 response criteria. Defined as bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absences of extramedullary disease; ANC \>= 1.0 x10\^9/L; platelet count \>=100 x 10\^9/L
次要结局
- Maximum Serum Concentration (Cmax) of Cusatuzumab(Cycle 1 Day 3)
- Percentage of Participants With CR With Partial Hematological Recovery (CRh)(Up to 3 years and 5 months)
- Overall Response Rate (ORR)(Up to 3 years and 5 months)
- Duration of First Response(Up to 3 years and 5 months)
- Percentage of Participants With CR With Incomplete Recovery (CRi)(Up to 3 years and 5 months)
- Percentage of Participants With CR Without MRD(Up to 3 years and 5 months)
- Time to First Response(Up to 3 years and 5 months)
- Red Blood Cell (RBC) and/or Platelets Transfusion Independence(Up to 3 years and 5 months)
- Cusatuzumab Minimum Serum Concentration (Cmin)(Cycle 1 Day 3)
- Percentage of Participants With CR Plus CRh(Up to 3 years and 5 months)
- Percentage of Participants With Negative MRD Who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)(Up to 3 years and 5 months)
- Number of Participants With Anti-cusatuzumab Antibodies(Up to 3 years and 5 months)