MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia
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|ClinicalTrials.gov Identifier: NCT00462605|
Recruitment Status : Completed
First Posted : April 19, 2007
Results First Posted : April 17, 2017
Last Update Posted : July 18, 2017
|Condition or disease||Intervention/treatment||Phase|
|Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Minimally Differentiated Myeloid Leukemia (M0) Adult Acute Monoblastic Leukemia (M5a) Adult Acute Monocytic Leukemia (M5b) Adult Acute Myeloblastic Leukemia With Maturation (M2) Adult Acute Myeloblastic Leukemia Without Maturation (M1) Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Acute Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Chronic Myelomonocytic Leukemia de Novo Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Refractory Anemia Refractory Anemia With Excess Blasts Refractory Anemia With Ringed Sideroblasts Refractory Cytopenia With Multilineage Dysplasia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Untreated Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Myeloid Leukemia||Drug: entinostat Drug: sargramostim||Phase 2|
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).
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.
III. Determine the toxicity profile of this regimen in these patients.
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.
Patients undergo blood and bone marrow (BM) collection at baseline and periodically during study for biologic correlative studies. Peripheral blood and bone marrow samples are assessed for changes in progenitor phenotype and clonogenic growth by flow cytometry and for changes in cytogenetics (i.e., malignant:nonmalignant cell ratio in BM CD34-positive cells, peripheral blood monocytes, peripheral blood neutrophils, and bone marrow and peripheral blood lymphoblasts) by FISH. Terminal differentiation of CD34-positive progenitor cells is studied in vitro in long-term cultures.
After completion of study therapy, patients are followed periodically for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||April 2007|
|Actual Primary Completion Date :||March 2011|
|Actual Study Completion Date :||March 2011|
Experimental: 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.
- Response (Complete and Partial Response) in Patients With Myeloid Disorders [ Time Frame: 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.
- Clinical Activity Assessed by Change in Peripheral Blood Counts [ Time Frame: Baseline and after 2 cycles ]
- Clinical Activity Assessed by Change in Transfusion Requirements [ Time Frame: Baseline and after 2 cycles ]
- Changes in Detectable Chromosomal Abnormalities Measured by Fluorescent in Situ Hybridization (FISH) [ Time Frame: Baseline and 6, 12, 24, and 36 weeks ]
- Change in the Percentage of Cells With Normal and Abnormal Myeloid Phenotype Measured by Flow Cytometry [ Time Frame: Baseline and 6, 12, 24, and 36 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00462605
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21287-8936|
|Principal Investigator:||B. Smith||Johns Hopkins University|