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MS-275 in Treating Patients With Hematologic Cancer

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ClinicalTrials.gov Identifier: NCT00015925
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : March 10, 2010
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE May 6, 2001
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date March 10, 2010
Study Start Date  ICMJE February 2001
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00015925 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
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 in Treating Patients With Hematologic Cancer
Official Title  ICMJE Phase I Clinical-Labratory Study of the Histone Deacetylase (HDA) Inhibitor MS-275 in Adults With Refractory and Relapsed Hematologic Malignancies
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of MS-275 in treating patients who have hematologic cancer.

Detailed Description

OBJECTIVES:

  • Determine the toxic effects and pharmacokinetics of MS-275 in patients with poor-risk hematologic malignancy.
  • Determine whether this drug induces changes in hematologic differentiation, in terms of changes in morphology, cell surface marker expression, and acetylation status, in these patients.
  • Determine whether this drug induces clinical response in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral MS-275 on days 1, 8, 15, and 22. Courses repeat every 6 weeks 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. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 25-30 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
Intervention  ICMJE Drug: entinostat
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   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
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • One of the following histologically confirmed diagnoses:

    • Acute myeloid leukemia (AML)

      • Newly diagnosed de novo AML in patients over 60 years old with the following poor-risk features:

        • Antecedent hematologic disorder
        • Complex karyotype or other adverse cytogenetics
        • Stem cell immunophenotype
      • AML arising from myelodysplastic syndromes (MDS)
      • Secondary AML
      • Relapsed or refractory AML, including primary induction failure
    • MDS

      • Poor-risk, defined as the following:

        • International Performance Score at least 1.5
        • More than 10% marrow blasts
        • Cytopenias in at least 2 lineages
      • Refractory anemia with excess blasts (RAEB)
      • RAEB in transformation
      • Chronic myelomonocytic leukemia
    • Acute lymphoblastic leukemia (ALL)

      • Newly diagnosed de novo ALL in patients over 60 years old with the following poor-risk features:

        • Complex karyotype or other adverse cytogenetics
        • Mixed lineage immunophenotype
      • Relapsed or refractory ALL, including primary induction failure
    • Chronic myelogenous leukemia (CML)

      • CML in accelerated phase or blast crisis
      • Interferon-refractory CML in chronic phase
    • Multiple myeloma (MM)

      • Relapsed or refractory, including prior autologous stem cell transplantation
    • Acute promyelocytic leukemia

      • Prior treatment with tretinoin
      • Ineligible for arsenic trioxide
      • No evidence of active coagulopathy
      • Low-risk for developing clinically significant coagulopathy during study

        • Low tumor burden by marrow aspiration at time of relapse
        • No prior coagulation-related sequelae (deep vein thrombosis, pulmonary embolism, or CNS thrombosis or bleed)
  • Failure after primary induction therapy or relapse after complete remission allowed if patient received no more than 3 courses of prior induction/reinduction therapy
  • Not eligible for curative stem cell transplantation
  • No hyperleukocytosis with at least 50,000/mm^3 leukemic blasts
  • No active CNS leukemia
  • No plasma cell leukemia
  • No amyloidosis resulting in major organ dysfunction

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics
  • No disseminated intravascular coagulation
  • No hyperviscosity

Hepatic:

  • AST/ALT no greater than 2 times normal
  • Alkaline phosphatase no greater than 2 times normal
  • Bilirubin no greater than 1.5 times normal

Renal:

  • Creatinine no greater than 1.5 times normal
  • No uncorrected hypercalcemia

Cardiovascular:

  • See Disease Characteristics
  • LVEF at least 45% by MUGA or echocardiogram
  • No intrinsic impaired cardiac function, including any of the following:

    • Myocardial infarction within the past 3 months
    • Prior severe coronary artery disease
    • Cardiomyopathy
    • Congestive heart failure

Other:

  • No active uncontrolled infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics
  • At least 1 week since prior growth factors (epoetin alfa, filgrastim [G-CSF], sargramostim [GM-CSF], interleukin [IL]-3, or IL-11)
  • At least 4 weeks since prior autologous stem cell transplantation
  • No prior allogeneic stem cell transplantation
  • No concurrent immunotherapy

Chemotherapy:

  • See Disease Characteristics
  • At least 3 weeks since prior chemotherapy and recovered
  • At least 24 hours since prior hydroxyurea or mercaptopurine for prevention of leukostasis
  • No concurrent chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 2 weeks since prior emergency radiotherapy to large soft tissue or lytic bony lesions for MM
  • No concurrent radiotherapy

Surgery:

  • Not specified

Other:

  • At least 24 hours since other prior noncytotoxic agents for prevention of leukostasis
  • No other concurrent antitumor therapy
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 NCT00015925
Other Study ID Numbers  ICMJE CDR0000068574, J0253
U01CA069854 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
JHOC-J0253
MSGCC-0050
NCI-2791
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Judith E. Karp, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date March 2010

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