Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

FR901228 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI UCCRC-12209B NCI-5965, NCT00062075, 5965

Objectives

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

Entry 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

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

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

Expected Enrollment

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

Outcomes

Response rate (complete and partial)
Toxicity

Correlation of clinical response with specific cytogenetic abnormalities

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.

Trial Contact Information

Trial Lead Organizations

University of Chicago Cancer Research Center

Olatoyosi Odenike, MD, Protocol chair		Ph: 773-702-3354; 888-824-0200 Email: todenike@medicine.bsd.uchicago.edu

Registry Information
Official Title		A Phase II Study Of Depsipeptide In Patients With Relapsed Or Refractory AML
Trial Start Date		2003-04-28
Registered in ClinicalTrials.gov		NCT00062075
Date Submitted to PDQ		2003-04-22
Information Last Verified		2006-12-10
NCI Grant/Contract Number		N01-CM17102, P30-CA14599