Romidepsin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 2 Study of Depsipeptide in Patients With Relapsed or Refractory AML

This phase II trial is studying how well romidepsin works in treating patients with relapsed or refractory acute myeloid leukemia. Drugs used in chemotherapy, such as romidepsin, work in different ways to stop tumor cells from dividing so they stop growing or die.

Study Overview

• Status: Completed
• Conditions: Recurrent Adult Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
• Intervention / Treatment: Drug: romidepsin

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the complete and partial response rate in patients with relapsed or refractory acute myeloid leukemia treated with FR901228 (depsipeptide).

II. Determine the toxicity of this drug in these patients. III. Correlate clinical response with specific cytogenetic abnormalities in patients treated with this drug.

OUTLINE: 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 romidepsin IV over 4 hours on days 1, 8, and 15.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Anticipated): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Comprehensive Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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,
  • Acute promyelocytic leukemia that has relapsed despite prior tretinoin and arsenic therapy,
  • Primary refractory AML for which no standard therapy exists
• 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
• Not medically appropriate for OR refused curative bone marrow or stem cell transplantation
• No CNS leukemia
• ECOG 0-2 OR Karnofsky 60-100%
• 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
• 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 psychiatric illness or social situation that would preclude study compliance
• No ongoing or active infection
• 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
• At least 2 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas)
• No concurrent chemotherapy, concurrent hydroxyurea allowed during the first course of study therapy to control hyperleukocytosis
• No concurrent radiotherapy
• 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
• No prior FR901228 (depsipeptide)
• At least 2 weeks since prior radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Patients receive romidepsin IV over 4 hours on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: romidepsin; Given IV; Other Names: FK228; FR901228; Istodax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate (complete and partial)	Up to 7 years
Adverse events, measured using National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0	Up to 7 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Primary Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: June 5, 2003
• First Submitted That Met QC Criteria: June 5, 2003
• First Posted (Estimate): June 6, 2003

Study Record Updates

• Last Update Posted (Estimate): December 4, 2015
• Last Update Submitted That Met QC Criteria: December 3, 2015
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Antineoplastic Agents; Antibiotics, Antineoplastic; Romidepsin
• Other Study ID Numbers: NCI-2009-00034; N01CM62201 (U.S. NIH Grant/Contract); P30CA014599 (U.S. NIH Grant/Contract); N01CM17102 (U.S. NIH Grant/Contract); U01CA099177 (U.S. NIH Grant/Contract); 12209B; CDR0000304460