6-Hydroxymethylacylfulvene in Treating Patients With Refractory Myelodysplastic Syndrome, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Blastic Phase Chronic Myelogenous Leukemia

NCT ID: NCT00003997

Last Updated: 2013-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-07-31

Brief Summary

Phase I trial to study the effectiveness of 6-hydroxymethylacylfulvene in treating patients who have refractory myelodysplastic syndrome, acute myeloid leukemia, acute lymphocytic leukemia, or blastic phase chronic myelogenous leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose for 6-hydroxymethylacylfulvene in patients with refractory myelodysplastic syndrome, acute myeloid leukemia, acute lymphocytic leukemia, or blastic phase chronic myelogenous leukemia.

II. Determine the qualitative and quantitative toxicities of this treatment in these patients.

III. Determine the duration and reversibility of the qualitative and quantitative toxicities of this treatment in these patients.

IV. Evaluate, in a preliminary manner, the antileukemic activity of this treatment in these patients.

V. Assess relative mRNA levels of selected NER genes (ERCC1, ERCC2, and ERCC3) in tumor tissues of patients treated with this regimen and correlate with clinical outcome.

OUTLINE: This is a dose escalation study.

Patients receive 6-hydroxymethylacylfulvene (HMAF) IV over 5 minutes on days 1-5. Treatment repeats every 3-4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3 patients receive escalating doses of HMAF. The maximum tolerated dose is defined as the dose at which dose limiting toxicity occurs in at least 40% of patients.

Patients are followed every 3 months for 1 year and then every 6 months thereafter.

Conditions

Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive 6-hydroxymethylacylfulvene (HMAF) IV over 5 minutes on days 1-5. Treatment repeats every 3-4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3 patients receive escalating doses of HMAF. The maximum tolerated dose is defined as the dose at which dose limiting toxicity occurs in at least 40% of patients.

Group Type: EXPERIMENTAL

irofulven

Intervention Type: DRUG

Interventions

irofulven

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• No candidates for curative therapies such as allogeneic bone marrow transplantation

PATIENT CHARACTERISTICS:

• Age: 18 and over
• Performance status: Zubrod 0-2
• Bilirubin no greater than 1.5 mg/dL
• Creatinine no greater than 1.5 mg/dL OR creatinine clearance at least 60 mL/min
• No active congestive heart failure
• No uncontrolled angina
• No myocardial infarction within past 6 months
• No concurrent grade 4 infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No overt psychosis, mental disability, or other incompetency that would preclude obtaining informed consent
• No life threatening nonmalignant illness

PRIOR CONCURRENT THERAPY:

• At least 2 weeks since prior biologic therapy and recovered
• No concurrent systemic anticancer biologic therapy
• At least 2 weeks since other prior chemotherapy and recovered
• Concurrent hydroxyurea allowed if needed to control blast counts
• No concurrent systemic anticancer chemotherapy
• At least 2 weeks since prior endocrine therapy and recovered
• Concurrent corticosteroids allowed if needed to control blast counts
• At least 2 weeks since prior radiotherapy and recovered
• No concurrent systemic radiotherapy
• No concurrent surgery
• At least 3 weeks since other prior investigational drugs (including analgesics or antiemetics) and recovered
• No other concurrent investigational drugs

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francis J. Giles, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

MDA-ID-99060

Identifier Type: -

Identifier Source: secondary_id

NCI-T99-0043

Identifier Type: -

Identifier Source: secondary_id

CDR0000067207

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02309

Identifier Type: -

Identifier Source: org_study_id