A Phase IA/II Multicenter, Dose-escalation Study of Oral AMN107 on a Continuous Daily Dosing Schedule in Adult Patients With Imatinib-resistant/Intolerant CML in Chronic or Accelerated Phase or Blast Crisis, Relapsed/Refractory Ph+ ALL, and Other Hematologic Malignancies.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 507
- 试验地点
- 25
- 主要终点
- Number of Participants With Major Cytogenetic Response (MCyR)
研究概览
简要总结
The purpose of this trial is to assess the efficacy, safety, tolerability, biologic activity, and pharmacokinetics of AMN107 in six groups of patients with one of the following conditions:
Relapsed/refractory Ph+ Acute lymphoblastic leukemia (ALL) (arm 1)
Group A - Imatinib failure only (arms 2, 3 and 4)
- imatinib-resistant or intolerant CML - Chronic Phase (CP)
- imatinib-resistant or intolerant CML - Accelerated Phase (AP)
- imatinib-resistant or intolerant CML - Blast Crisis (BC)
Group B - Imatinib and other TKI failure (arms 2, 3 and 4)
- imatinib-resistant or intolerant CML - Chronic Phase (CP)
- imatinib-resistant or intolerant CML - Accelerated Phase (AP)
- imatinib-resistant or intolerant CML - Blast Crisis (BC)
Hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) (arm 5)
Systemic mastocytosis (Sm) (arm 6)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Main inclusion criteria include:
- •Patients with CML in blast crisis, CML in accelerated phase defined as never in blast crisis phase, or CML in chronic phase defined as never been in blast crisis phase or accelerated phase who have: *developed progressive disease during therapy with at least 600 mg of imatinib per day, -OR- *patients with CML on imatinib therapy, at any dose, developing progressive disease and the presence of a genetic mutation likely to result in imatinib resistance -OR- *have developed an intolerance to imatinib
- •Relapsed or refractory Ph+ ALL
- •Hypereosinophilic syndrome/chronic eosinophilic leukemia.
- •Systemic mastocytosis who have a clinical indication for treatment.
- •Prior imatinib therapy for patients with Ph+ ALL, HES/CEL and SM is permitted but is not required
- •CML patients who have been treated with an investigational tyrosine kinase inhibitor who otherwise meet the definition of imatinib-resistance or intolerance are eligible
- •Written informed consent prior to any study procedures being performed
排除标准
- •Impaired cardiac function
- •Patients with severe/chronic or uncontrolled medical conditions (including but not limited to diabetes, infections, GI impairment, CNS infiltration, liver and kidney disease)
- •Prior and concomitant use of certain medications (including but not limited to warfarin, chemotherapy, hematopoietic colony-stimulating growth factors, medications that can affect electrocardiogram test results, other investigational drugs )
- •Women who are pregnant or breastfeeding
- •Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
- •Patients unwilling to comply with the protocol.
- •Known diagnosis of human immunodeficiency virus (HIV) infection
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
CML-CP With Prior Imatinib Only
Imatinib-resistant / intolerant PH+ CML-CP patients
干预措施: Nilotinib (Drug)
CML-AP With Prior Imatinib Onl
Imatinib-resistant / intolerant PH+ CML-AP patients
干预措施: Nilotinib (Drug)
CML-CP
Imatinib-resistant / intolerant PH+ CML-CP patients
干预措施: Nilotinib (Drug)
结局指标
主要结局
Number of Participants With Major Cytogenetic Response (MCyR)
时间窗: Up to End of the Treatment (Approximately 7.5 years)
Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in bone marrow).
Number of Participants Confirmed Overall Hematological Response (Phase II)
时间窗: Up to End of the Treatment (Approximately 7.5 years)
Hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count \<10 x 109/L, Platelet count \<450 x 109/L, Basophils \<5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes \< 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver). Hematological response was a primary outcome measure for Arm CML-AP with prior imatinib only.
次要结局
- Number of Participants With Complete Hematologic Response (Phase II)(Up to End of the Treatment (Approximately 7.5 years))
- Participants With (MMR) Major Molecular Response (Phase II)(Up to End of the Treatment (Approximately 7.5 years))
- Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety(From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years))
- Number of Participants With Overall Major Cytogenetic Responses (Phase II)(Up to End of the Treatment (Approximately 7.5 years))
- Overall Survival (OS) (Phase II)(Up to End of the Treatment (Approximately 7.5 years))
- Time to Progression (TTP) (Phase II)(Up to End of the Treatment (Approximately 7.5 years))