A Phase II Study of and Oral Histone Deacytylase Inhibitor, MS-275 (NSC 706995), in Combination With Sargramostim (GM-CSF, Berlex, Inc.) Treating Relapsed and Refractory Myeloid Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Response (Complete and Partial Response) in Patients With Myeloid Disorders
研究概览
简要总结
This phase II trial is studying how well giving MS-275 together with GM-CSF works in treating patients with myelodysplastic syndrome and/or relapsed or refractory acute myeloid leukemia. MS-275 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving MS-275 together with GM-CSF may be an effective treatment for myelodysplastic syndrome and acute myeloid leukemia
详细描述
PRIMARY OBJECTIVE:
I. Determine clinical response in patients with myelodysplastic syndromes and/or relapsed or refractory acute myeloid leukemia or acute lymphocytic leukemia treated with MS-275 in combination with sargramostim (GM-CSF).
SECONDARY OBJECTIVES:
I. Determine the clinical activity of this regimen, in terms of changes in peripheral blood counts and changes in individual patient transfusion requirements, in these patients.
II. Determine the biologic activity of this regimen, in terms of changes in the peripheral blood and bone marrow phenotype (i.e., induction of markers of myeloid differentiation or lymphoid differentiation) and changes in detectable cytogenetic abnormalities in the blood and marrow compartments, in these patients.
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
- •Diagnosis of 1 of the following diseases by bone marrow aspiration and/or biopsy:
- •Myelodysplastic syndromes (MDS) meeting the following criteria:
- •Must have 1 of the following subtypes:
- •Refractory anemia (RA) (no RA with 5q-syndrome),
- •RA with ringed sideroblasts or
- •Refractory cytopenia with multilineage dysplasia
- •Myelodysplastic syndromes (MDS) meeting the following criteria:
- •Must have 1 of the following subtypes:
- •Refractory cytopenia with multilineage dysplasia and ringed sideroblasts,
- •RA with excess blasts (RAEB)-1, RAEB-2,
- •Myelodysplastic syndromes, unclassified or
- •Chronic myelomonocytic leukemia
- •International Prognostic Scoring System score of intermediate-2 or high-risk
- •Acute myeloid leukemia (AML) meeting 1 of the following criteria:
- •Relapsed or refractory AML, including any of the following subtypes:
- •* AML with recurrent cytogenetic abnormalities (i.e., AML with 11q23 [MLL] abnormalities)
- •AML with multilineage dysplasia
- •AML that is therapy-related
- •AML, not otherwise categorized (M0 [minimally differentiated], M1 [without maturation], M2 [with maturation], M4 [myelomonocytic leukemia], M5 [monoblastic/monocytic leukemia], M6 [erythroid leukemia], and M7 [megakaryoblastic leukemia])
- •Untreated AML
- •Newly diagnosed patients are eligible provided they do not qualify for potentially curative intensive chemotherapeutic regimens
- •Acute lymphocytic leukemia (ALL) meeting 1 of the following criteria:
- •Relapsed or refractory ALL
- •Patients with any measurable residual disease are eligible, including cytogenetic abnormalities
- •Untreated ALL
- •Newly diagnosed patients are eligible provided they do not qualify for potentially curative intensive chemotherapeutic regimens, including any of the following:
- •Patients who have refused chemotherapy for untreated ALL
- •Patients who are deemed to be poor candidates medically for ALL induction chemotherapy
- •Relatively stable bone marrow function for > 7 days prior to study entry
- •WBC count that has not doubled within the past 7 days
- •WBC =<10,000/mm³
- •No uncontrolled peripheral leukemia (i.e., blast count > 30,000/mm³)
- •No active CNS disease
- •Lumbar puncture with negative cytology required for patients with clinical symptoms of active CNS disease
- •Not a candidate for a potentially curative allogeneic stem cell transplantation OR considered a poor candidate for such a procedure due to age, medical comorbidities, or lack of a suitable donor
- •Hemoglobin >= 8 g/dL (transfusions allowed)
- •Creatinine =< 2.0 mg/dL
- •Bilirubin =< 1.6 mg/dL (unless secondary to hemolysis)
- •AST or ALT =< 3 times upper limit of normal (unless disease-related)
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No untreated or progressive infections
- •No history of intolerance to sargramostim (GM-CSF)
- •Recovered from all treatment-related toxicities
- •More than 2 weeks since prior therapy for AML, ALL, or MDS, including chemotherapy, hematopoietic growth factors, or biologic therapy such as monoclonal antibodies
- •Concurrent hydroxyurea allowed during course 1 for control of leukocytosis if WBC > 30,000/mm³
- •ECOG performance status 0-2
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral MS-275 on days 1, 8, 15, and 22. Patients also receive sargramostim (GM-CSF) subcutaneously once daily on days 1-42 in courses 3 and 5 and on days 1-35 in courses 1, 2, 4, and 6. Treatment repeats every 6 weeks for 2-6 courses in the absence of disease progression or unacceptable toxicity. After completion of 2 courses of study therapy, patients who achieve a complete or partial response may receive an additional 4 courses. Patients who maintain stable disease for more than 2 months after completion of 6 courses of study therapy may receive an additional 6 courses at the time of disease progression, provided they meet original eligibility criteria.
干预措施: entinostat (Drug)
Arm I
Patients receive oral MS-275 on days 1, 8, 15, and 22. Patients also receive sargramostim (GM-CSF) subcutaneously once daily on days 1-42 in courses 3 and 5 and on days 1-35 in courses 1, 2, 4, and 6. Treatment repeats every 6 weeks for 2-6 courses in the absence of disease progression or unacceptable toxicity. After completion of 2 courses of study therapy, patients who achieve a complete or partial response may receive an additional 4 courses. Patients who maintain stable disease for more than 2 months after completion of 6 courses of study therapy may receive an additional 6 courses at the time of disease progression, provided they meet original eligibility criteria.
干预措施: sargramostim (Drug)
结局指标
主要结局
Response (Complete and Partial Response) in Patients With Myeloid Disorders
时间窗: Up to 2 years
Response to treatment was assessed after two cycles, according to International Working Group (IWG) criteria. Cytogenetic responses were monitored in patients with abnormalities at baseline.
次要结局
- Changes in Detectable Chromosomal Abnormalities Measured by Fluorescent in Situ Hybridization (FISH)(Baseline and 6, 12, 24, and 36 weeks)
- Clinical Activity Assessed by Change in Peripheral Blood Counts(Baseline and after 2 cycles)
- Clinical Activity Assessed by Change in Transfusion Requirements(Baseline and after 2 cycles)
- Change in the Percentage of Cells With Normal and Abnormal Myeloid Phenotype Measured by Flow Cytometry(Baseline and 6, 12, 24, and 36 weeks)