NCT00015925CompletedPhase 1
Phase I Clinical-Labratory Study of the Histone Deacetylase (HDA) Inhibitor MS-275 in Adults With Refractory and Relapsed Hematologic Malignancies
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins2 sites in 1 countryStarted: February 1, 2001Last updated:
Conditions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Locations
- 2
Study Overview
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.
Study Design
- Study Type
- Interventional
- Primary Purpose
- Treatment
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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:
- •18 and over
- •Performance status:
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •See Disease Characteristics
- •No disseminated intravascular coagulation
- •No hyperviscosity
- •AST/ALT no greater than 2 times normal
- +36 more not shown
Exclusion Criteria
- Not provided
Investigators
Study Sites (2)
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