Mitomycin and Mitoxantrone in Treating Patients With Acute Myelogenous Leukemia
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Purpose
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Some cancers become resistant to chemotherapy drugs. Combining mitomycin with a chemotherapy drug may reduce resistance to the drug and allow the cancer cells to be killed.
PURPOSE: Phase I trial to study the effectiveness of mitomycin and mitoxantrone in treating patients with acute myelogenous leukemia and to determine whether mitomycin can reduce the cancer's resistance to chemotherapy.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia |
Biological: sargramostim Drug: mitomycin C Drug: mitoxantrone hydrochloride |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Primary Purpose: Treatment |
| Official Title: | 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 |
| Estimated Enrollment: | 29 |
| Study Start Date: | September 1996 |
| Study Completion Date: | August 2000 |
| Primary Completion Date: | August 2000 (Final data collection date for primary outcome measure) |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, New Hampshire | |
| Norris Cotton Cancer Center | |
| Lebanon, New Hampshire, United States, 03756 | |
| Study Chair: | Christopher H. Lowrey, MD | Norris Cotton Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | Dartmouth-Hitchcock Medical Center |
| ClinicalTrials.gov Identifier: | NCT00003003 History of Changes |
| Other Study ID Numbers: | CDR0000065565, P30CA023108, DMS-9614, NCI-V97-1260 |
| Study First Received: | November 1, 1999 |
| Last Updated: | March 1, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by Dartmouth-Hitchcock Medical Center:
|
recurrent adult acute myeloid leukemia secondary acute myeloid leukemia |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Neoplasms by Histologic Type Neoplasms Mitomycins Mitomycin Mitoxantrone Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses |
Pharmacologic Actions Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Alkylating Agents Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Central Nervous System Agents |
ClinicalTrials.gov processed this record on May 19, 2013