A Pilot Clinical Trial of Mitomycin C Modulation of Multidrug Resistance Proteins and a Phase I Evaluation of Mitomycin C and Mitoxantrone in Patients With Acute Myelogenous Leukemia
18 Years
N/A
Both
Leukemia
Trial Information
A Pilot Clinical Trial of Mitomycin C Modulation of Multidrug Resistance Proteins and a Phase I Evaluation of Mitomycin C and Mitoxantrone in Patients With Acute Myelogenous Leukemia
OBJECTIVES: I. Determine whether a single mitomycin C treatment will suppress expression of
one or more proteins associated with the multidrug resistance phenotype in leukemia cells of
patients with refractory acute myelogenous leukemia. II. Determine the maximum tolerated
dose of a combination of mitomycin C followed 72 hours later by a single dose of
mitoxantrone in patients with acute myelogenous leukemia with GM-CSF support. III. Determine
the toxicity profile and pharmokinetics for these combinations of mitomycin C and
mitoxantrone. IV. Determine the ability of this regimen to induce complete response in
patients with primary resistant or refractory acute myelogenous leukemia.
OUTLINE: Patients receive mitomycin C by IV bolus on day 1 of treatment. Patients receive
mitoxantrone beginning on day 4. One patient each is entered at the first and second dose
levels. Dose escalation of mitoxantrone continues in the absence of toxicity. If the patient
experiences toxicity at level 1 or 2, then 2 additional patients are entered at that tier.
Three patients are entered at all subsequent tiers. At these tiers, if no toxicity is
observed, escalation continues. If 1 of the 3 patients experiences toxicity, an additional 3
patients are enrolled at the same dose. If none of these additional patients experiences
toxicity, escalation continues; however, if 1 patient has toxicity, the trial is stopped. If
2 or more have toxicities, the dose is de-escalated. If 2 or more of the original 3 patients
have toxicities, the dose is de-escalated. On day 15, patients are treated with sargramostim
(GM-CSF) intravenously over 4 hours if the bone marrow is free of residual leukemia; GM-CSF
treatment continues until the ANC is greater than 1,500/mm3 for 3 consecutive days.
PROJECTED ACCRUAL: For the pilot study of mitomycin C modulation of multidrug resistance
proteins, 12 patients will be accrued. For the phase I study of mitomycin C and
mitoxantrone, at least 17 patients will be entered.
Inclusion Criteria
DISEASE CHARACTERISTICS: Acute myelogenous leukemia, either de novo or secondary (evolving
from myelodysplastic syndrome, myeloproliferative syndrome, or previous treatment for
malignancies other than leukemia) OR Refractory anemia with excess blasts in
transformation Patient is at least 60 years old and at least one of the following is true:
Failed one induction attempt or First or greater relapse OR Patient is 18-59 years old
without an acceptable allogeneic donor and no autologous marrow for transplant and at
least one of the following is true: Failed 2 separate induction attempts, or Second or
greater relapse, or Resistant relapse, or Relapsed post transplant Prior treatment with
anthracyclines or mitoxantrone required Cumulative daunorubicin dose less than 400/m2
required
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70%-100% (50% if
hospitalized) Hematopoietic: Not specified Hepatic: Total direct bilirubin no greater than
2.0 mg/dL SGOT and SGPT no greater than 3 x normal Alkaline phosphatase no greater than 3
x normal No active hepatitis Renal: Not specified Cardiovascular: No myocardial infarction
within last 6 months No congestive heart failure Ejection fraction greater than 50%
(measured by MUGA or 2-D Echo) Pulmonary: No severe chronic obstructive pulmonary disease
Other: No active infection or antimicrobiologically stabilized infection Not pregnant
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease
Characteristics Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not
specified
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Christopher H. Lowrey, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Norris Cotton Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000065565
NCT ID:
NCT00003003
Start Date:
September 1996
Completion Date:
August 2000
Related Keywords:
- Leukemia
- recurrent adult acute myeloid leukemia
- secondary acute myeloid leukemia
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
Name | Location |
|---|---|
| Norris Cotton Cancer Center | Lebanon, New Hampshire 03756 |
