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)


Phase 1
18 Years
N/A
Not Enrolling
Both
Leukemia, Myelodysplastic Syndromes

Thank you

Trial Information

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)


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Francis J. Giles, MD

Investigator Role:

Study Chair

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02309

NCT ID:

NCT00003997

Start Date:

July 1999

Completion Date:

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • recurrent adult acute myeloid leukemia
  • recurrent adult acute lymphoblastic leukemia
  • blastic phase chronic myelogenous leukemia
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • Blast Crisis
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location
University of Texas - MD Anderson Cancer Center Houston, Texas  77030-4009