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
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
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response (complete and partial response) in patients with myeloid disorders
Up to 2 years
Johns Hopkins University
United States: Food and Drug Administration
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