Mitomycin and Mitoxantrone in Treating Patients With Acute Myelogenous Leukemia

March 15, 2018 updated by: Christopher H. Lowrey, Dartmouth-Hitchcock Medical Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

29

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Norris Cotton Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dartmouth-Hitchcock Medical Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Christopher H. Lowrey, MD, Norris Cotton Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 1996

Primary Completion (Actual)

August 1, 2000

Study Completion (Actual)

August 1, 2000

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

August 11, 2004

First Posted (Estimate)

August 12, 2004

Study Record Updates

Last Update Posted (Actual)

March 19, 2018

Last Update Submitted That Met QC Criteria

March 15, 2018

Last Verified

June 1, 2000

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000065565
  • P30CA023108 (U.S. NIH Grant/Contract)
  • DMS-9614
  • NCI-V97-1260

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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