A Randomized Phase 2/3 Study of DACOGEN® (Decitabine) Plus Talacotuzumab (JNJ-56022473; Anti CD123) Versus DACOGEN (Decitabine) Alone in Patients With AML Who Are Not Candidates for Intensive Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 326
- 主要终点
- Part B: Percentage of Participants Who Achieved Complete Response (Complete Response Rate) Based on Investigator Assessment
研究概览
简要总结
The primary objective of study Part A is to assess the safety of talacotuzumab (formerly CSL362) monotherapy and confirm the recommended Phase 2 dose (RP2D) in participants with acute myeloid leukemia (AML) for whom experimental therapy is appropriate. The primary objective of study Part B are to assess complete response (CR) rate and overall survival (OS) in participants with AML who are not eligible for intense induction chemotherapy and who are randomly assigned to receive decitabine plus talacotuzumab at the RP2D or decitabine alone.
详细描述
This is a 2-part, open-label, multicenter, Phase 2/3 study conducted in participants with AML who are suitable for experimental therapy (Part A) and in participants with untreated AML who are not eligible for intense induction chemotherapy or hematopoeitic stem cell transplantation (HSCT) (Part B). In Study Part A, the safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile will be assessed to confirm the RP2D of 9 milligram per kilogram (mg/kg) talacotuzumab. In Study Part B, participants will be randomized in a 1:1 ratio into either decitabine + talacotuzumab (arm 1) or decitabine alone (arm 2). Blood and bone marrow sampling will be done in Part A and B for disease assessment, PK, PD, and biomarkers will be collected in all participants. Safety will be monitored throughout the study.
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
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •De novo or secondary acute myeloid leukemia (AML) (post myelodysplastic syndrome [MDS] or myeloproliferative neoplasm [MPN] or after leukemogenic chemotherapy) according to WHO 2008 criteria
- •For Part A:
- •Participants With AML: treatment naive or relapsed for whom experimental therapy is appropriate (as assessed by their treating physician)
- •For Part B:
- •Greater than or equal to (>=) 75 years of age or >= 65 up to 75 years of age and have at least one of the following: congestive heart failure or ejection fraction less than or equal to (<=) 50 percent; creatinine greater than (>) 2 milligram per deciliter (mg/dL); dialysis or prior renal transplant; documented pulmonary disease with lung diffusing capacity for carbon monoxide (DLCO) <= 65 percent of expected, or forced expiratory volume in 1 second (FEV1) <= 65 percent of expected or dyspnea at rest requiring oxygen; eastern cooperative oncology group (ECOG) performance status of 2; prior or current malignancy that does not require concurrent treatment; unresolved infection; 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
- •Previously untreated AML (except: emergency leukopheresis and/or hydroxyurea during the screening phase to control hyperleukocytosis but must be discontinued at least one day prior to start of study therapy)
- •Not eligible for an allogeneic hematopoietic stem cell transplantation
- •ECOG Performance Status score of 0, 1 or 2
- •A woman must be either: Not of childbearing potential: postmenopausal (more than [>] 45 years of age with amenorrhea for at least 12 months; If, of childbearing potential must be practicing a highly effective method of birth control
- •A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening
- •A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository for at least 3 months after last study treatment
排除标准
- •Acute promyelocytic leukemia with t(15;17), or its molecular equivalent (PML-RARalpha)
- •For Part B only: Known leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system
- •Participants who received prior treatment with a hypomethylating agent
- •For Part A only: Participants who did not recover from all clinically significant toxicities (excluding alopecia and hematologic toxicities) of any previous surgery, radiotherapy, targeted therapy, or chemotherapy to less than or equal to Grade 1
- •Any uncontrolled active systemic infection that requires treatment with intravenous (IV) antibiotics
- •A history of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV if tested at screening
- •Active systemic hepatitis infection requiring treatment or other clinically active liver disease
研究组 & 干预措施
Decitabine plus Talacotuzumab
Part A: For Cycle 1 of Part A, participants will receive talacotuzumab on Day 1. Starting from Cycle 2 of Part A, participants may receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle.
Part B Arm 1: Participants will receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle.
干预措施: Decitabine 20 mg/m^2 (Drug)
Decitabine plus Talacotuzumab
Part A: For Cycle 1 of Part A, participants will receive talacotuzumab on Day 1. Starting from Cycle 2 of Part A, participants may receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle.
Part B Arm 1: Participants will receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle.
干预措施: Talacotuzumab 9 mg/kg (Drug)
Decitabine
Participants in Part B Arm 2 will receive decitabine on Day 1,2, 3, 4 and 5 of a 28-day cycle.
干预措施: Decitabine 20 mg/m^2 (Drug)
结局指标
主要结局
Part B: Percentage of Participants Who Achieved Complete Response (Complete Response Rate) Based on Investigator Assessment
时间窗: Approximately up to 2.5 years
Complete response rate defined as percentage of participants who achieved complete response as per modified International Working Group (IWG) criteria. CR: Bone marrow blasts less than (\<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (\>)1.0\*10\^9/liter (L) (1000/micro liter \[mcL\]); platelet count \>100\*10\^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.
Part B: Overall Survival
时间窗: Approximately up to 2.5 years
Overall Survival (OS) was defined as the time from the date of randomization to date of death from any cause. Median Overall Survival was estimated by using the Kaplan-Meier method. This endpoint is reported here for Part B only as per the planned analysis.
次要结局
- Part B: Percentage of Participants With Complete Response (CR) Plus Minimal Residual Disease (MRD) Negative Complete Response With Incomplete Recovery (CRi)(Approximately 2.5 years)
- Part B: Event-free Survival (EFS) Based on Investigator Assessment(Approximately up to 2.5 years)
- Part B: Percentage of Participants Who Achieved CR and CRi (Overall Response Rate)(Approximately up to 2.5 years)
- Part B: Time to Best Response(Approximately 2.5 years)
- Part B: Duration of Response (DOR) Based on Investigator Assessment(Approximately 2.5 years)