- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00015925
MS-275 in Treating Patients With Hematologic Cancer
Phase I Clinical-Labratory Study of the Histone Deacetylase (HDA) Inhibitor MS-275 in Adults With Refractory and Relapsed Hematologic Malignancies
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.
Study Overview
Status
Conditions
Intervention / Treatment
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
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21231
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
-
Baltimore, Maryland, United States, 21201
- Greenebaum Cancer Center at University of Maryland Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- refractory anemia with excess blasts
- refractory anemia with excess blasts in transformation
- chronic myelomonocytic leukemia
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- secondary acute myeloid leukemia
- chronic phase chronic myelogenous leukemia
- recurrent adult acute myeloid leukemia
- untreated adult acute myeloid leukemia
- atypical chronic myeloid leukemia
- myelodysplastic/myeloproliferative disease, unclassifiable
- blastic phase chronic myelogenous leukemia
- relapsing chronic myelogenous leukemia
- refractory multiple myeloma
- recurrent adult acute lymphoblastic leukemia
- accelerated phase chronic myelogenous leukemia
- untreated adult acute lymphoblastic leukemia
- adult acute promyelocytic leukemia (M3)
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Precancerous Conditions
- Syndrome
- Myelodysplastic Syndromes
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Leukemia
- Preleukemia
- Plasmacytoma
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Histone Deacetylase Inhibitors
- Entinostat
Other Study ID Numbers
- CDR0000068574, J0253
- P30CA006973 (U.S. NIH Grant/Contract)
- U01CA069854 (U.S. NIH Grant/Contract)
- JHOC-J0253
- MSGCC-0050
- NCI-2791
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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