Randomized Phase II Study Comparing Two Administration Schedules of Flavopiridol (Alvocidib, NSC 649890, IND 46, 211) Given in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone Hydrochloride for Adults With Newly Diagnosed, Previously Untreated, Poor Risk Acute Myelogenous Leukemias (AML)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 2
- 主要终点
- Complete Response
研究概览
简要总结
This randomized phase II trial is studying two different schedules of alvocidib to compare how well they work when given together with cytarabine and mitoxantrone in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as alvocidib, cytarabine, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known which schedule of alvocidib is more effective when given together with cytarabine and mitoxantrone in treating patients with acute myeloid leukemia.
详细描述
PRIMARY OBJECTIVES:
I. To compare the efficacy of two different schedules (bolus vs "hybrid bolus-infusion") of alvocidib followed by cytarabine and mitoxantrone hydrochloride in patients with newly diagnosed acute myeloid leukemia (AML) with poor-risk features.
SECONDARY OBJECTIVES:
I. To compare the toxicities of these regimens. II. To determine the disease-free survival and overall survival of patients who demonstrate a response to these regimens.
III. To compare the pharmacokinetics of alvocidib when administered in two different schedules (bolus vs "hybrid bolus-infusion").
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
- •Pathologically confirmed newly diagnosed acute myeloid leukemia (AML) meeting the following criteria:
- •Subtypes M0, M1, M2, M4-7
- •No acute promyelocytic leukemia (M3)
- •At least 50 years of age OR >= 18 years of age with >= 1 of the following poor-risk disease features:
- •Antecedent hematologic disorder, including myelodysplastic syndromes (MDS)-related AML or prior myeloproliferative disorder (MPD)
- •Treatment-related AML, AML with trilineage dysplasia
- •Myeloid sarcoma, myeloid proliferations related to Down Syndrome, or blastic plasmacytoid dendritic cell neoplasm
- •AML with trilineage dysplasia
- •AML with adverse cytogenetics (defined as -5/-5q; -7/-7q; abnormal 3q, 9q, 11q, 20q, 21q, or 17p; t[6;9]; t[9;22]; trisomy 8; trisomy 13, complex karyotypes [>= 3 unrelated abnormalities]),
- •No hyperleukocytosis with >= 50,000 blasts/uL (leukapheresis or hydroxyurea allowed for cytoreduction immediately prior to the first dose of alvocidib)
- •No active CNS leukemia
- •ECOG performance status 0-2
- •Serum creatinine =< 2.0 mg/dL
- •ALT/AST =< 5 times upper limit of normal
- •Bilirubin =< 2.0 mg/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •No active uncontrolled infection
- •Infection that is under active treatment allowed provided it is controlled with antibiotics
- •No other life-threatening illness
- •No mental deficits and/or psychiatric history that would preclude giving informed consent or following study requirements
- •At least 24 hours since prior leukapheresis or hydroxyurea for cytoreduction
- •Prior non-cytotoxic therapies (e.g., thalidomide or lenalidomide, interferon, cytokines, low-dose 5-azacytidine, or low-dose cytoxan) for MDS or MPD allowed
- •Prior chemotherapy or bone marrow/stem cell transplantation for non-AML malignancy allowed
- •No prior alvocidib
- •No other concurrent chemotherapy, radiotherapy, or immunotherapy
- •No other concurrent investigational or commercially-available antitumor therapies for AML
- •LVEF >= 45%
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.
干预措施: laboratory biomarker analysis (Other)
Arm I
Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.
干预措施: alvocidib (Drug)
Arm I
Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.
干预措施: mitoxantrone hydrochloride (Drug)
Arm I
Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.
干预措施: cytarabine (Drug)
Arm I
Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.
干预措施: pharmacological study (Other)
Arm II
Patients receive alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 1-3. Patients also receive cytarabine and mitoxantrone hydrochloride as in arm I.
干预措施: alvocidib (Drug)
Arm II
Patients receive alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 1-3. Patients also receive cytarabine and mitoxantrone hydrochloride as in arm I.
干预措施: mitoxantrone hydrochloride (Drug)
Arm II
Patients receive alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 1-3. Patients also receive cytarabine and mitoxantrone hydrochloride as in arm I.
干预措施: cytarabine (Drug)
Arm II
Patients receive alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 1-3. Patients also receive cytarabine and mitoxantrone hydrochloride as in arm I.
干预措施: pharmacological study (Other)
Arm II
Patients receive alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 1-3. Patients also receive cytarabine and mitoxantrone hydrochloride as in arm I.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Complete Response
时间窗: 1 year
Bone marrow showing less than 5% leukemic blasts with normal maturation of all cell lines, an ANC of at least 1000/uL and a platelet count of 100,000/uL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. Repeat marrow confirmation 4-6 weeks following the marrow documenting CR is not required due to the need for continued treatment in CR.
次要结局
- Number of Participants Experiencing Death From Any Cause Within 60 Days of Starting FLAM(60 days)
- Disease-free Survival(up to 2 years)