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Mitomycin and Mitoxantrone in Treating Patients With Acute Myelogenous Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00003003
Recruitment Status : Completed
First Posted : August 12, 2004
Last Update Posted : March 19, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Christopher H. Lowrey, Dartmouth-Hitchcock Medical Center

Brief Summary:

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 or disease Intervention/treatment Phase
Leukemia Biological: sargramostim Drug: mitomycin C Drug: mitoxantrone hydrochloride Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
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
Study Start Date : September 1996
Actual Primary Completion Date : August 2000
Actual Study Completion Date : August 2000

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00003003

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United States, New Hampshire
Norris Cotton Cancer Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
National Cancer Institute (NCI)
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Study Chair: Christopher H. Lowrey, MD Norris Cotton Cancer Center
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Responsible Party: Christopher H. Lowrey, Hematology Oncologist, Dartmouth-Hitchcock Medical Center Identifier: NCT00003003    
Other Study ID Numbers: CDR0000065565
P30CA023108 ( U.S. NIH Grant/Contract )
First Posted: August 12, 2004    Key Record Dates
Last Update Posted: March 19, 2018
Last Verified: June 2000
Keywords provided by Christopher H. Lowrey, Dartmouth-Hitchcock Medical Center:
recurrent adult acute myeloid leukemia
secondary acute myeloid leukemia
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Alkylating Agents
Nucleic Acid Synthesis Inhibitors