Phase I Study of a Pharmacologically Derived Hybrid Bolus-Infusion Schedule of Flavopiridol (NSC 649890, IND 46,211) Given in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose determined by dose-limiting toxicities graded according to NCI-CTC version 3.0
研究概览
简要总结
Drugs used in chemotherapy, such as flavopiridol, 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. Giving a new schedule of more than one drug (combination chemotherapy) may kill more cancer cells. This phase I trial is studying the side effects, best dose, and best schedule for flavopiridol when given together with cytarabine and mitoxantrone in treating patients with relapsed or refractory acute leukemia.
详细描述
OBJECTIVES:
I. Determine the toxicities of escalating doses of flavopiridol administered by "hybrid" bolus-infusion schedule and given in timed sequence with cytarabine and mitoxantrone hydrochloride in patients with refractory or relapsed acute leukemia.
II. Determine the incidence of clinical response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of flavopiridol. Patients receive flavopiridol IV over 30 minutes on days 1, 2, and 3.
Patients receive cytarabine IV continuously over 72 hours beginning on day 6 and mitoxantrone hydrochloride IV over 60-120 minutes on day 9. Treatment repeats every 35-63 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Pathologically confirmed acute myeloid leukemia or acute lymphoblastic leukemia:
- •Relapsed >= 1 time OR refractory disease:
- •Patients who fail primary induction therapy or who relapse after achieving complete remission are eligible if they have received =< 3 prior courses of induction/reinduction therapy
- •Relapsed >= 1 time OR refractory disease
- •Patients who fail primary induction therapy or who relapse after achieving complete remission are eligible if they have received =< 3 prior courses of induction/reinduction therapy
- •No active CNS leukemia
- •ECOG performance status 0-2
- •AST and ALT =< 5 times upper limit normal (ULN)
- •Alkaline phosphatase =< 5 times ULN
- •Bilirubin =< 2.0 mg/dL
- •Creatinine =< 2.0 mg/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •LVEF >= 45% by MUGA or ECHO
- •No active, uncontrolled infection
- •No other life-threatening illness
- •No mental deficits and/or psychiatric history that would preclude study compliance
- •No active graft-vs-host disease
- •Recovered from all prior therapies
- •At least 24 hours since prior hydroxyurea, steroids, imatinib mesylate, arsenic trioxide, interferon, or leukapheresis for blast count control
- •At least 4 weeks since prior stem cell transplantation (autologous or allogeneic)
- •At least 4 days since prior growth factors
- •At least 3 weeks since prior chemotherapy, except for non-aplasia producing treatments (e.g., low-dose cyclophosphamide, hydroxyurea, interferon, imatinib mesylate, mercaptopurine, thalidomide, azacitidine, or decitabine)
- •No prior flavopiridol
- •No other concurrent chemotherapy, radiotherapy, or immunotherapy
- •No acute promyelocytic leukemia (M3)
- •No hyperleukocytosis with > 50,000 blasts/mm^3
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive flavopiridol IV over 30 minutes on days 1, 2, and 3. Patients receive cytarabine IV continuously over 72 hours beginning on day 6 and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.
干预措施: alvocidib (Drug)
Arm I
Patients receive flavopiridol IV over 30 minutes on days 1, 2, and 3. Patients receive cytarabine IV continuously over 72 hours beginning on day 6 and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.
干预措施: cytarabine (Drug)
Arm I
Patients receive flavopiridol IV over 30 minutes on days 1, 2, and 3. Patients receive cytarabine IV continuously over 72 hours beginning on day 6 and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.
干预措施: mitoxantrone hydrochloride (Drug)
Arm I
Patients receive flavopiridol IV over 30 minutes on days 1, 2, and 3. Patients receive cytarabine IV continuously over 72 hours beginning on day 6 and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximum tolerated dose determined by dose-limiting toxicities graded according to NCI-CTC version 3.0
时间窗: Up to 63 days
次要结局
未报告次要终点