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

NCT00462605 | Completed Phase 2 Results DMC

• 3 other identifiers: NCI-2009-00195J06114U01CA070095
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Response (Complete and Partial Response) in Patients With Myeloid Disorders

  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.

  Up to 2 years

Secondary Outcomes (4)

• 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

• Changes in Detectable Chromosomal Abnormalities Measured by Fluorescent in Situ Hybridization (FISH)

  Baseline and 6, 12, 24, and 36 weeks

• Change in the Percentage of Cells With Normal and Abnormal Myeloid Phenotype Measured by Flow Cytometry

  Baseline and 6, 12, 24, and 36 weeks

Study Arms (1)

Arm I

EXPERIMENTAL

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.

Drug: entinostat; Drug: sargramostim

Interventions

entinostat DRUG

Given PO

Also known as: HDAC inhibitor SNDX-275, SNDX-275

Arm I

sargramostim DRUG

Given SC

Also known as: GM-CSF, Leukine, Prokine

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Myelomonocytic, Chronic; Myeloproliferative Disorders; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts

Interventions

entinostat; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Anemia; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: B. Douglas Smith
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

smithdo@jhmi.edu

410-614-5068

Study Officials

• B. Smith

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2007
• First Posted: April 19, 2007
• Study Start: April 1, 2007
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: July 18, 2017
• Results First Posted: April 17, 2017

Record last verified: 2017-06

Locations

US (1)