Clinical Trial: MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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

Detailed Summary:

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.

III. Determine the toxicity profile of this regimen in these patients.

OUTLINE:

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.

  • Clinical Activity Assessed by Change in Peripheral Blood Counts and Transfusion Requirements [ Time Frame: Baseline and weekly after treatment administered ]
  • 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 ]


    • Original Secondary Outcome:

    • Improvement of peripheral blood counts
    • Changes in transfusion requirements
    • In vivo induction of terminal differentiation of myeloid progenitor cells as assessed by flow cytometry
    • In vivo changes in detectable chromosomal abnormalities as assessed by FISH


    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: April 18, 2007
    Date Started: April 2007
    Date Completion:
    Last Updated: March 6, 2017
    Last Verified: March 2017