We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00101179
First Posted: January 10, 2005
Last Update Posted: October 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
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.

Condition Intervention Phase
Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia de Novo Myelodysplastic Syndrome Leukemia Myelodysplastic Syndrome Previously Treated Myelodysplastic Syndrome Recurrent Adult Acute Myeloid Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndrome Untreated Adult Acute Myeloid Leukemia Drug: Azacitidine Drug: Entinostat Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Dose-Finding Trial of the Histone Deacetylase Inhibitor MS-275 (NSC 706995) in Combination With 5-Azacitidine (5AC, NSC 102816) in Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMMoL) and Acute Myeloid Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of MS-275 in combination with 5-azacitidine, assessed using Common Toxicity Criteria version 3.0 [ Time Frame: 4 weeks ]

Secondary Outcome Measures:
  • Levels of histone acetylation and gene re-expression [ Time Frame: 4 weeks ]
  • Optimal dose combination [ Time Frame: At study completion ]
  • Response rate measured by IWG criteria [ Time Frame: 16 weeks ]

Enrollment: 63
Actual Study Start Date: November 3, 2004
Primary Completion Date: April 30, 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

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: Azacitidine
Given SC
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza
Drug: Entinostat
Given orally
Other Names:
  • HDAC inhibitor SNDX-275
  • MS 27-275
  • MS-275
  • SNDX-275

Detailed Description:

OBJECTIVES:

I. Determine the safety and toxicity of MS-275 and azacitidine in patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.

II. Determine the maximum tolerated dose and optimal phase II dose of MS-275 when combined with azacitidine in these patients.

III. Determine, preliminarily, the potential therapeutic activity of this regimen in these patients.

IV. Correlate MS-275 pharmacokinetics with clinical response and laboratory correlative endpoints in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of MS-275. 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.

[Note: Patients who do not achieve hematologic improvement or partial or complete response but who have stable disease after 4 courses of therapy may receive an additional 4 courses of therapy at a higher dose than what was originally assigned]

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Acute promyelocytic leukemia allowed provided patient is in at least second relapse and has already received treatment regimens containing arsenic trioxide and isotretinoin
  • No clinical evidence of CNS or pulmonary leukostasis or CNS leukemia
  • Peformance status:

    • Zubrod 0-2
  • Life expectancy:

    • At least 6 months
  • Hematopoietic:

    • See Disease Characteristics

      • Hemoglobin ≥ 8 g/dL (transfusion allowed)
      • No disseminated intravascular coagulation
  • Renal:

    • Creatinine normal OR
    • Creatinine clearance >= 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study treatment
  • No untreated, active infection
  • No other serious or uncontrolled medical condition
  • More than 3 weeks since prior hematopoietic growth factors for this malignancy
  • At least 3 weeks since prior hydroxyurea (2 weeks for AML patients)
  • No concurrent hydroxyurea
  • Recovered from all prior therapy
  • At least 2 weeks since prior cytotoxic therapy (AML patients)
  • More than 3 weeks since other prior therapy for this malignancy
  • No other concurrent investigational or commercial agents or therapies for this malignancy
  • No concurrent valproic acid
  • Hepatic:

    • Bilirubin normal unless due to hemolysis or Gilbert's syndrome
    • AST and ALT =< 2.5 times upper limit of normal
  Contacts and Locations
Information from the National Library of Medicine

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): NCT00101179


Locations
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, New York
Mount Sinai Hospital
New York, New York, United States, 10029
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Steven Gore Johns Hopkins University/Sidney Kimmel Cancer Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00101179     History of Changes
Other Study ID Numbers: NCI-2009-00071
NCI-2009-00071 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000405841
J0443
J0443 ( Other Identifier: Johns Hopkins University/Sidney Kimmel Cancer Center )
6591 ( Other Identifier: CTEP )
P30CA006973 ( U.S. NIH Grant/Contract )
U01CA070095 ( U.S. NIH Grant/Contract )
First Submitted: January 7, 2005
First Posted: January 10, 2005
Last Update Posted: October 25, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Neoplasm Metastasis
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplastic Processes
Myelodysplastic-Myeloproliferative Diseases
Azacitidine
Entinostat
Histone Deacetylase Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors