A Phase II Randomized Trial of Carboplatin and Topotecan; Flavopiridol, Mitoxantrone and Cytosine Arabinoside; and Sirolimus, Mitoxantrone, Etoposide and Cytosine Arabinoside for the Treatment of Adults With Primary Refractory or Initial Relapse of Acute Myelogenous Leukemia (AML)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 92
- 试验地点
- 20
- 主要终点
- The Rate of Complete Remission (CR+CRi)
研究概览
简要总结
This randomized phase II trial is comparing three different combination chemotherapy regimens to see how well they work in treating patients with relapsed or refractory acute myeloid leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating patients with relapsed or refractory acute myeloid leukemia.
详细描述
PRIMARY OBJECTIVES:
I. To determine the complete remission (CR) + cytogenic complete remission (CRc) + morphologic complete remission with incomplete blood count recovery (CRi) rate of carboplatin and topotecan; flavopiridol, mitoxantrone and cytosine arabinoside and sirolimus, mitoxantrone, etoposide and cytosine arabinoside in adult patients with refractory or relapsed acute myeloid leukemia (AML).
NOTE: Since the CRc patients are required to be either CR or CRi, we only report the rate of CR+CRi in the results section.
II. To determine the rate of treatment failure of these regimens. III. To determine the incidence and severity of toxicities of these regimens. IV. To analyze the predictive value of blast cell properties that have been suggested to determine response. (Correlative laboratory studies) V. To determine whether pretreatment levels of B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (Bcl-2) or, alternatively, whether a therapy-induced change in topoisomerase I levels correlates with response to this regimen. (Correlative laboratory studies) VI. To assess the impact of clonal evolution by comparing cytogenetic abnormalities at the time of relapse with those at initial diagnosis and correlating these abnormalities and changes with response to the treatment regimens in this protocol. (Cytogenetic and fluorescent in situ hybridization [FISH] studies) VII. Panel FISH studies for common AML rearrangements will be performed on relapse AML specimens to determine the presence of these recurrent AML abnormalities and to evaluate for subtle additional abnormalities consistent with clonal evolution in these relapse specimens. (Cytogenetic and FISH studies)
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm A (carboplatin and topotecan hydrochloride)
Patients receive carboplatin and topotecan hydrochloride IV continuously over 24 hours on days 1-5.
干预措施: carboplatin (Drug)
Arm A (carboplatin and topotecan hydrochloride)
Patients receive carboplatin and topotecan hydrochloride IV continuously over 24 hours on days 1-5.
干预措施: topotecan hydrochloride (Drug)
Arm B (alvocidib, mitoxantrone, cytarabine)
Patients receive alvocidib IV over 4.5 hours QD on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9.
干预措施: alvocidib (Drug)
Arm B (alvocidib, mitoxantrone, cytarabine)
Patients receive alvocidib IV over 4.5 hours QD on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9.
干预措施: mitoxantrone hydrochloride (Drug)
Arm B (alvocidib, mitoxantrone, cytarabine)
Patients receive alvocidib IV over 4.5 hours QD on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9.
干预措施: cytarabine (Drug)
Arm C (sirolimus, mitoxantrone, etoposide, cytarabine)
Patients receive sirolimus PO QD on days 2-9, mitoxantrone hydrochloride IV over 15 minutes QD, etoposide IV over 1 hour QD, and cytarabine IV over 3 hours QD on days 4-8 or 5-9. (Closed to accrual)
干预措施: mitoxantrone hydrochloride (Drug)
Arm C (sirolimus, mitoxantrone, etoposide, cytarabine)
Patients receive sirolimus PO QD on days 2-9, mitoxantrone hydrochloride IV over 15 minutes QD, etoposide IV over 1 hour QD, and cytarabine IV over 3 hours QD on days 4-8 or 5-9. (Closed to accrual)
干预措施: cytarabine (Drug)
Arm C (sirolimus, mitoxantrone, etoposide, cytarabine)
Patients receive sirolimus PO QD on days 2-9, mitoxantrone hydrochloride IV over 15 minutes QD, etoposide IV over 1 hour QD, and cytarabine IV over 3 hours QD on days 4-8 or 5-9. (Closed to accrual)
干预措施: sirolimus (Drug)
Arm C (sirolimus, mitoxantrone, etoposide, cytarabine)
Patients receive sirolimus PO QD on days 2-9, mitoxantrone hydrochloride IV over 15 minutes QD, etoposide IV over 1 hour QD, and cytarabine IV over 3 hours QD on days 4-8 or 5-9. (Closed to accrual)
干预措施: etoposide (Drug)
结局指标
主要结局
The Rate of Complete Remission (CR+CRi)
时间窗: Assessed every 3 months for the first 2 years and then every 6 months until relapse or death up to 3 years from registration.
CR requires: 1. peripheral blood counts: neutrophil count ≥ 1.0 x 10\^9/L, platelet count ≥ 100 x 10\^9/L, reduced hemoglobin concentration or hematocrit has no bearing on remission status, and leukemic blasts must not be present in the peripheral blood. 2. bone marrow aspirate and biopsy: maturation of all cell lines must be present, ≤ 5% blasts, auer rods must not be detectable. 3. extramedullary leukemia, such as central nervous system (CNS) or soft tissue involvement, must not be present. CRi requires that all criteria for complete remission be satisfied except patients can have residual neutropenia (\<1 x 10\^9/L) or thrombocytopenia (\<100 x 10\^9/L).
次要结局
- The Rate of Treatment Failure(Assessed every 3 months for the first 2 years and then every 6 months until relapse or death up to 3 years from registration.)