MS-275 in Treating Patients With Hematologic Cancer

NCT ID: NCT00015925

Last Updated: 2010-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-02-28

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.

Conditions

Leukemia; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Study Design

• Primary Study Purpose: TREATMENT

Interventions

entinostat

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Principal Investigators

Judith E. Karp, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

U01CA069854

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0253

Identifier Type: -

Identifier Source: secondary_id

MSGCC-0050

Identifier Type: -

Identifier Source: secondary_id

NCI-2791

Identifier Type: -

Identifier Source: secondary_id

CDR0000068574, J0253

Identifier Type: -

Identifier Source: org_study_id