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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00003997

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Drug: irofulven	Phase 1

Detailed Description

OBJECTIVES:

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.
Determine the qualitative and quantitative toxicities of this treatment in these patients.
Determine the duration and reversibility of the qualitative and quantitative toxicities of this treatment in these patients.
Evaluate, in a preliminary manner, the antileukemic activity of this treatment in these patients.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study of MGI-114 (NSC#683863) in Patients With Refractory Myelodysplastic Syndromes, Acute Leukemia and Chronic Myelogenous Leukemia in Blastic Phase (CML-BP)

Study Start Date :

Jul 1, 1999

Actual Primary Completion Date :

Oct 1, 2000

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: irofulven

Arm

Intervention/Treatment

Experimental: Arm I

Drug: irofulven

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of refractory myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), acute lymphocytic leukemia, or blastic phase chronic myelogenous leukemia MDS and AML include:
First salvage with primary refractory disease or first complete remission of no more than 12 months
Second or greater salvage
After the maximum tolerated dose is determined, AML patients with an intermediate prognosis (i.e., complete remission of more than 12 months, but less than 24 months) are eligible
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