NCT00101179

Brief Summary

MS-275 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving MS-275 together with azacitidine may kill more cancer cells. This phase I trial is studying the side effects and best dose of MS-275 when given together with azacitidine in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
63

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2004

Longer than P75 for phase_1

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 3, 2004

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

January 7, 2005

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 10, 2005

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 20, 2011

Completed
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 3, 2014

Completed
Last Updated

October 18, 2019

Status Verified

October 1, 2019

Enrollment Period

6.5 years

First QC Date

January 7, 2005

Last Update Submit

October 17, 2019

Conditions

Acute Myeloid LeukemiaChronic Myelomonocytic Leukemiade Novo Myelodysplastic SyndromeLeukemiaMyelodysplastic SyndromeRecurrent Adult Acute Myeloid LeukemiaSecondary Acute Myeloid LeukemiaSecondary Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose of MS-275 in combination with 5-azacitidine, assessed using Common Toxicity Criteria version 3.0

    4 weeks

Secondary Outcomes (3)

  • Response rate measured by IWG criteria

    16 weeks

  • Optimal dose combination

    At study completion

  • Levels of histone acetylation and gene re-expression

    4 weeks

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive azacitidine subcutaneously on days 1-10 and oral MS-275 on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses\* of MS-275 until the maximum tolerated dose (MTD) is determined. Patients receive adjusted doses of azacitidine based on clinical response. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 9 additional patients are treated at the MTD.

Drug: AzacitidineDrug: Entinostat

Interventions

AzacitidineDRUG

Given SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza
Arm I
EntinostatDRUG

Given orally

Also known as: HDAC inhibitor SNDX-275, MS 27-275, MS-275, SNDX-275
Arm I

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of 1 of the following:
  • Histologically confirmed myelodysplastic syndromes (MDS) by bone marrow aspiration and/or biopsy
  • International Prognostic Scoring System (IPSS) score of intermediate-1, intermediate-2, or high
  • International Prognostic Scoring System (IPSS) score of intermediate-1, intermediate-2, or high
  • Low IPSS score allowed provided patient has a clinically significant cytopenia (i.e., absolute neutrophil count \< 1,000/mm\^3, untransfused hemoglobin \< 8 g/dL, platelet count \< 20,000/mm\^3, or anemia requiring transfusion)
  • Chronic myelomonocytic leukemia
  • Acute myeloid leukemia (AML)
  • Relapsed or refractory disease
  • Untreated AML allowed provided patient meets \>= 1 of the following criteria:
  • Age 60 and over
  • AML arising in the setting of an antecedent hematologic disorder
  • High-risk cytogenetic abnormalities
  • Medical conditions that may compromise the ability to give cytotoxic chemotherapy as the primary modality
  • Refused cytotoxic chemotherapy
  • WBC \< 30,000/mm3 for \>= 2 weeks before study entry
  • +29 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (3)

  • Prebet T, Sun Z, Ketterling RP, Zeidan A, Greenberg P, Herman J, Juckett M, Smith MR, Malick L, Paietta E, Czader M, Figueroa M, Gabrilove J, Erba HP, Tallman MS, Litzow M, Gore SD; Eastern Cooperative Oncology Group and North American Leukemia intergroup. Azacitidine with or without Entinostat for the treatment of therapy-related myeloid neoplasm: further results of the E1905 North American Leukemia Intergroup study. Br J Haematol. 2016 Feb;172(3):384-91. doi: 10.1111/bjh.13832. Epub 2015 Nov 18.

    PMID: 26577691DERIVED

  • Figueroa ME, Skrabanek L, Li Y, Jiemjit A, Fandy TE, Paietta E, Fernandez H, Tallman MS, Greally JM, Carraway H, Licht JD, Gore SD, Melnick A. MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation. Blood. 2009 Oct 15;114(16):3448-58. doi: 10.1182/blood-2009-01-200519. Epub 2009 Aug 3.

    PMID: 19652201DERIVED

  • Fandy TE, Herman JG, Kerns P, Jiemjit A, Sugar EA, Choi SH, Yang AS, Aucott T, Dauses T, Odchimar-Reissig R, Licht J, McConnell MJ, Nasrallah C, Kim MK, Zhang W, Sun Y, Murgo A, Espinoza-Delgado I, Oteiza K, Owoeye I, Silverman LR, Gore SD, Carraway HE. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. Blood. 2009 Sep 24;114(13):2764-73. doi: 10.1182/blood-2009-02-203547. Epub 2009 Jun 22.

    PMID: 19546476DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteLeukemia, Myelomonocytic, ChronicLeukemiaMyelodysplastic Syndromes

Interventions

Azacitidineentinostat

Condition Hierarchy (Ancestors)

Leukemia, MyeloidNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesMyelodysplastic-Myeloproliferative DiseasesBone Marrow DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Study Officials

  • Steven D Gore

    Johns Hopkins University/Sidney Kimmel Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 7, 2005

First Posted

January 10, 2005

Study Start

November 3, 2004

Primary Completion

April 20, 2011

Study Completion

February 3, 2014

Last Updated

October 18, 2019

Record last verified: 2019-10

Locations

US(3)