Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT00101179
Recruitment Status : Completed
First Posted : January 10, 2005
Last Update Posted : October 18, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE January 7, 2005
First Posted Date  ICMJE January 10, 2005
Last Update Posted Date October 18, 2019
Actual Study Start Date  ICMJE November 3, 2004
Actual Primary Completion Date April 20, 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2013)
Maximum tolerated dose of MS-275 in combination with 5-azacitidine, assessed using Common Toxicity Criteria version 3.0 [ Time Frame: 4 weeks ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2018)
  • Response rate measured by IWG criteria [ Time Frame: 16 weeks ]
  • Optimal dose combination [ Time Frame: At study completion ]
  • Levels of histone acetylation and gene re-expression [ Time Frame: 4 weeks ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia
Official Title  ICMJE 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)
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.
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]

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • de Novo Myelodysplastic Syndrome
  • Leukemia
  • Myelodysplastic Syndrome
  • Recurrent Adult Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Secondary Myelodysplastic Syndrome
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.

Interventions:
  • Drug: Azacitidine
  • Drug: Entinostat
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 7, 2015)
63
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE February 3, 2014
Actual Primary Completion Date April 20, 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00101179
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Steven D Gore Johns Hopkins University/Sidney Kimmel Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP