MS-275 in Treating Patients With Hematologic Cancer

Leukemia Clinical Trial

Official title:

Phase I Clinical-Labratory Study of the Histone Deacetylase (HDA) Inhibitor MS-275 in Adults With Refractory and Relapsed Hematologic Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00015925
• Other study ID #: CDR0000068574, J0253
• Secondary ID: U01CA069854P30CA
• Status: Completed
• Phase: Phase 1
• First received: May 6, 2001
• Last updated: March 9, 2010
• Start date: February 2001

Study information

• Verified date: March 2010
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Plasmacytoma
• Preleukemia

Intervention

Drug:
• entinostat

Locations

Country	Name	City	State
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,