FR901228 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia - Full Text View

Sponsor:	University of Chicago
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00062075

Purpose

RATIONALE: Drugs used in chemotherapy, such as FR901228, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory acute myeloid leukemia.

Condition	Intervention	Phase
Leukemia	Drug: romidepsin	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Study Of Depsipeptide In Patients With Relapsed Or Refractory AML

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: FR 901228

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Response rate (complete and partial) [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Correlation of clinical response with specific cytogenetic abnormalities [ Designated as safety issue: No ]

Estimated Enrollment:	47
Study Start Date:	April 2003

Detailed Description:

OBJECTIVES:

Determine the complete and partial response rate in patients with relapsed or refractory acute myeloid leukemia treated with FR901228 (depsipeptide).
Determine the toxicity of this drug in these patients.
Correlate clinical response with specific cytogenetic abnormalities in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to the presence of a specific chromosomal abnormality (t[8;21] vs inv 16 vs t[15;17] vs absence of these chromosomal abnormalities).

Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 22-47 patients will be accrued for this study within 12-27 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed acute myeloid leukemia (AML) defined by the WHO classification
- Initial diagnosis with either of the following:
  - Bone marrow or peripheral blood myeloblasts of at least 20%
  - Recurring genetic abnormalities (e.g., t[8;21], inv 16, or t[16;16]) and bone marrow blast percentage less than 20%
Relapsed or refractory disease defined by 1 of the following:
- Under 60 years of age and in second relapse or greater
- Over 60 years of age and in first relapse
  - Patients who are over 60 years of age with previously untreated disease and who refuse conventional chemotherapy are eligible
  - Patients who are over 60 years of age and in first relapse and poor medical candidates for reinduction chemotherapy or who refuse conventional chemotherapy are eligible
- Acute promyelocytic leukemia that has relapsed despite prior tretinoin and arsenic therapy
- Primary refractory AML for which no standard therapy exists
Not medically appropriate for OR refused curative bone marrow or stem cell transplantation
No CNS leukemia

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2 OR
Karnofsky 60-100%

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Bilirubin no greater than 2 times upper limit of normal (ULN)
AST/ALT no greater than 3 times ULN

Renal

Creatinine no greater than 2 times ULN

Cardiovascular

LVEF at least 40% by MUGA
QTc interval less than 500 msec by EKG
No myocardial infarction within the past 3 months
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No prior allergic reactions attributed to compounds of similar chemical or biological composition to FR901228 (depsipeptide)
No concurrent uncontrolled illness
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
At least 4 weeks since prior autologous stem cell or bone marrow transplantation
No prior allogeneic stem cell or bone marrow transplantation
No concurrent biologic agents

Chemotherapy

See Disease Characteristics
At least 2 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas)
No prior FR901228 (depsipeptide)
No concurrent chemotherapy
- Concurrent hydroxyurea allowed during the first course of study therapy to control hyperleukocytosis

Endocrine therapy

Not specified

Radiotherapy

At least 2 weeks since prior radiotherapy
No concurrent radiotherapy

Surgery

Not specified

Other

Recovered from prior therapy
At least 4 weeks since prior investigational agents
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent investigational agents
No concurrent drugs known to have histone deacetylase inhibitor activity (e.g., sodium valproate)
No other concurrent antineoplastic agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00062075

Locations

United States, Illinois
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

University of Chicago

National Cancer Institute (NCI)

Investigators

Study Chair:

Olatoyosi M. Odenike, MD

University of Chicago

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Odenike OM, Alkan S, Sher D, Godwin JE, Huo D, Brandt SJ, Green M, Xie J, Zhang Y, Vesole DH, Stiff P, Wright J, Larson RA, Stock W. Histone deacetylase inhibitor romidepsin has differential activity in core binding factor acute myeloid leukemia. Clin Cancer Res. 2008 Nov 1;14(21):7095-101.

Study ID Numbers:	CDR0000304460, UCCRC-12209B, NCI-5965
Study First Received:	June 5, 2003
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00062075 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

adult acute promyelocytic leukemia (M3)
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia
adult acute myeloid leukemia with t(8;21)(q22;q22)

adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)

Additional relevant MeSH terms:

Leukemia
Neoplasms
Neoplasms by Histologic Type
Antineoplastic Agents
Therapeutic Uses

Romidepsin
Leukemia, Myeloid
Antibiotics, Antineoplastic
Leukemia, Myeloid, Acute
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 27, 2009