Phase II Study of Temozolomide in Previously Untreated Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) Subjects Unsuitable for Standard Induction Therapy Exhibiting Low MGMT Expression
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 主要终点
- Clinical Response at the End of Temozolomide Induction
研究概览
简要总结
The primary objective of this study is to evaluate the safety, tolerability, and efficacy of temozolomide in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) participants who are not candidates for standard induction therapy and exhibit low MGMT expression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Confirmed diagnosis of acute myeloid leukemia (AML), any subtype except acute promyelocytic leukemia (APL), by the World Health Organization (WHO) criteria, or high risk MDS with blasts between 10 and 20% in the bone marrow.
- •No prior AML chemotherapy except hydroxyurea.
- •Leukemic blast count <30x10^9/L at the start of therapy. Prior cytoreduction with hydroxyurea (maximum 14 days) is permitted.
- •Participant is not a candidate for aggressive induction based on at least one of the following: adverse-risk cytogenetics (complete or partial deletion of 5 or 7, complex [>3] cytogenetic abnormalities, inv3, 11q23 abnormalities); secondary AML (antecedent hematologic disorder or therapy-related AML); comorbid medical illnesses precluding standard induction therapy; participant's refusal of standard induction therapy.
- •Confirmed low MGMT expression (MGMT: beta-actin ≤0.2), as evaluated by Western blot, or weak MGMT expression defined as > 0.2 and ≤2.5 if promoter is methylated, upon Sponsor approval.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •Use of medically approved contraception in fertile males and females.
- •Negative urine or serum pregnancy test for women of childbearing potential (72 hours prior to Baseline).
排除标准
- •Serum bilirubin >2 times the upper limit of normal (ULN), or serum aspartate aminotransferase/ alanine aminotransferase >5 times ULN.
- •Serum creatinine >200 umol/L.
- •History of other malignancies within 1 year prior to study entry, with the exception of localized nonmelanomatous skin cancer or cervical cancer in situ.
- •Presence of active uncontrolled infection.
- •Known human immunodeficiency virus (HIV) infection.
- •Any medical condition that may interfere with protocol evaluation or oral medication intake.
- •Prior chemotherapy other than hydroxyurea.
研究组 & 干预措施
Temozolomide
Temozolomide capsules orally, once daily: 1 induction cycle (200 mg/m^2/day for 7 days in 1 28 day cycle), 1 consolidation cycle (200 mg/m^2/day for 7 days in 1 28 day cycle), then 200 mg/m^2/day for 7 days each 28-day cycle or for 5 days each 28-day cycle (12 cycle maximum). Alternatively participants could have received 100 mg/m^2/day for 21 days of each 28-day cycle (12 cycle maximum).
干预措施: temozolomide (Drug)
结局指标
主要结局
Clinical Response at the End of Temozolomide Induction
时间窗: at the end of each cycle (approximately 4 weeks post start of cycle), up to a maximum 63 weeks
Complete Response (CR): \< 5% blasts in normocellular bone marrow (BM); Absolute Neutrophil Count (ANC) \> 1.0 x 10\^9/L, platelets \> 100 x 10\^9/L, and no extramedullary disease. CR with incomplete platelet recovery (CRp): All the criteria of CR but with platelets \< 100 x 10\^9/L but ≥ 50 x 10\^9/L and platelet transfusion independent. Morphologic leukemia-free state (MLFS): complete clearance of blasts from marrow and blood, but criteria for CR or CRp not met. Partial response (PR): decrease ≥ 50% BM blasts. Minimal Response (MR): decrease ≥ 25% but \<50% BM blasts.
次要结局
- Duration of Response in Participants Achieving Complete Response (CR) and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide(Up to 1 year after treatment ends (up to 115 weeks))
- Relapse-free Survival in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide(Start of treatment until disease progression [up to 1 year after treatment ends (up to 115 weeks)])
- Overall Survival (OS) in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide(Start of treatment until death or end of study [up to 1 year after treatment ends (up to 115 weeks)])
- Number of Previously Untreated Participants With Low O6-Methylguanine Methyltransferase (MGMT) Expression(Baseline)
- MGMT Expression in Leukemic Blasts at the Time of Relapse(Up to 1 year after treatment ends (up to 115 weeks))
- Number of Participants With CR, PR, or MLFS Who Received Modified Low Dose Maintenance Therapy (100 mg/m^2/Day x21 Days of Each 28 Day Cycle) and Experienced Toxicity(From first dose to 30 days after last dose of study drug (up to 67 weeks))
- Progression-free Survival for Participants Achieving PR, MLSF, or MR(Start of treatment until disease progression [up to 1 year after treatment ends (up to 115 weeks)])
- Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-30(Baseline and post-study visit (63 weeks))
- Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by EORTC QLQ-LC13(Baseline and post-study visit (63 weeks))
- Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by Functional Assessment of Cancer Therapy (FACT)-G(Baseline and post-study visit (63 weeks))