An Extension to a Phase II Study to Determine the Safety and Anti-Leukemic Effects of STI571 in Adult Patients With Philadelphia Chromosome Positive Leukemia Including Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Accelerated Phase Chronic Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 293
- 试验地点
- 5
- 主要终点
- Percentage of Participants With Hematologic Response in Accelerated Phase Chronic Myeloid/Myelogenous Leukemia
研究概览
简要总结
The objectives of Part 1 of the study were:
- To determine the rate of hematologic response (HR) lasting ≥4 weeks in participants with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the accelerated phase (AP).
- To evaluate duration of HR, overall survival, cytogenetic response (CyR), time to blast crisis in CML participants in the AP, improvement of symptomatic parameters, tolerability and safety of STI571 treatment.
The objective of the extension (Part 2) was:
-To enable participants to have access to study drug and continue study treatment and to decrease data collection to include only overall survival and serious adverse events.
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
- •Male or female participants, aged ≥18 years, with a histologically confirmed diagnosis of Ph+ leukemia of one of the following types:
- •Accelerated phase chronic myeloid/myelogenous leukemia (CML).
- •Acute lymphoid/lymphoblastic leukemia (ALL) or acute myeloid/myelogenous leukemia (AML) in first or subsequent relapse after either standard chemotherapy, autologous or allogeneic bone marrow transplantation, or high-dose treatment with peripheral blood stem cell support, or
- •ALL or AML refractory to standard chemotherapy (no complete remission achieved after two courses of conventional induction chemotherapy).
- •Lymphoid blastic phase of CML in first or subsequent relapse or refractory to standard chemotherapy.
- •With serum serum glutamate oxaloacetate transaminase (aspartate aminotransferase) and serum glutamate pyruvate transaminase (alanine aminotransferase) not more than 3 x upper limit of normal (ULN) (or not more than 5xULN if clinically suspected leukemic involvement of the liver), serum creatinine concentration not more than 2xULN, and total serum bilirubin level not more than 3xULN (bilirubin limit was 1.5xULN before protocol amendment 1)
排除标准
- •Participants who had an Eastern Cooperative Oncology Group (ECOG) performance status score ≥
- •Participants with known leukemic involvement of the central nervous system (CNS).
- •Participants who had received treatment with any of the following agents: interferon-alpha within 48 hours, hydroxyurea within 24 hours, homoharringtonine within 14 days, low-dose, moderate dose or high dose cytosine arabinoside within 7, 14 or 28 days respectively, 6-mercaptopurine, vinca alkaloids or steroids within 7 days, anthracyclines, mitoxantrone, etoposide, methotrexate, cyclophosphamide within 21 days, or busulfan within 6 weeks.
- •Participants who had undergone hematopoietic stem cell transplantation within six weeks of Day 1, or who had not achieved full hematopoietic recovery following the transplant.
- •Participants with grade 3/4 cardiac disease or any serious, concomitant, medical condition.
- •Participants with a history of non-compliance to medical regimens or who were considered potentially unreliable.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg
Participants with accelerated phase chronic myeloid/myelogenous leukemia received STI571 400 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.
干预措施: STI571 400 mg (Drug)
Lymphoid Blast Crisis 400 mg
Participants with lymphoid blast crisis received STI571 400 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.
干预措施: STI571 400 mg (Drug)
Acute Lymphoblastic Leukemia 400 mg
Participants with acute lymphoblastic leukemia received STI571 400 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.
干预措施: STI571 400 mg (Drug)
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg
Participants with accelerated phase chronic myeloid/myelogenous leukemia received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.
干预措施: STI571 600 mg (Drug)
Lymphoid Blast Crisis 600 mg
Participants with lymphoid blast crisis received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.
干预措施: STI571 600 mg (Drug)
Acute Lymphoblastic Leukemia 600 mg
Participants with acute lymphoblastic leukemia received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.
干预措施: STI571 600 mg (Drug)
Acute Myeloid/Myelogenous Leukemia 600 mg
Participants with acute myeloid/myelogenous leukemia received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.
干预措施: STI571 600 mg (Drug)
结局指标
主要结局
Percentage of Participants With Hematologic Response in Accelerated Phase Chronic Myeloid/Myelogenous Leukemia
时间窗: Up to 3 years after start of treatment
Hematologic response was evaluated from hematology measurements in the peripheral blood (PB) and bone marrow (BM) and assessments of extramedullary leukemic involvement (EMD) at physical examination. Response was defined as complete hematologic remission (CHR), no evidence of leukemia (NEL), or return to chronic phase (RTC).
次要结局
- Duration of Response in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia(Up to 3 years after start of treatment)
- Time to Progression to Blast Crisis in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia(Up to 3 years after start of treatment)
- Overall Survival by Disease(12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 months after start of treatment)
- Overall Survival by Dose in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia(12, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132 months after start of treatment)
- Percentage of Participants With Cytogenetic Response in Accelerated Phase Chronic Myeloid/Myelogenous Leukemia(Up to 3 years after start of treatment)
- Time to Response in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia(Up to 3 years after start of treatment)