Clofarabine and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia, or Myeloproliferative Disorders

May 5, 2010 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Adults and Children With Relapsed or Refractory Acute Leukemias

RATIONALE: Drugs used in chemotherapy, such as clofarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine and cyclophosphamide in treating patients with relapsed or refractory acute leukemia, chronic myelogenous leukemia, or myeloproliferative disorders.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the feasibility and tolerability of administering clofarabine and fractionated cyclophosphamide in patients with relapsed or refractory acute leukemia, chronic myelogenous leukemia, or high-risk myeloproliferative disorders
  • Determine the maximum tolerated dose of clofarabine and fractionated cyclophosphamide in these patients.
  • Determine the toxic effects of these drugs in these patients.

Secondary

  • Obtain preliminary data of biologic and pharmacodynamic effects of this regimen on marrow and circulating leukemic blasts in these patients.

OUTLINE: This is a dose-escalation study. Patients are stratified according to age (adult vs child).

Patients receive cyclophosphamide IV over 2 hours on day 0. Patients then receive clofarabine IV over 2 hours and cyclophosphamide IV over 2 hours on days 1-3 and 8-10. Treatment with clofarabine and cyclophosphamide repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of clofarabine and cyclophosphamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 10 patients are treated at the MTD.

After completion of study treatment, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

70

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
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

2 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed leukemia or myeloproliferative disorders, including 1 of the following:

    • Acute myeloid leukemia (AML) of any subtype

      • Treatment-related AML OR AML evolving from myeloproliferative disorders (MPD) or transformed from myelodysplastic syndrome
    • Acute lymphocytic leukemia

    • Acute progranulocytic leukemia

      • Must not be eligible for arsenic or retinoic acid therapy
    • Chronic myelogenous leukemia in accelerated phase or blast crisis

    • High-risk MPD, including any of the following:

      • Myelofibrosis
      • Chronic myelomonocytic leukemia with 5%-19% blasts
      • Relapsed or refractory juvenile myelomonocytic leukemia

  • Relapsed and/or refractory disease with progressive disease since last therapy

    • No more than 3 prior induction regimens with cytotoxic agents for adults
    • Must be in second relapse for patients < 21 years of age

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2 (for adults) OR Lansky 50-100% (for pediatric patients)
  • Bilirubin ≤ 1.5 mg/dL (may be elevated due to hemolysis in adult patients)
  • AST and ALT ≤ 5 times upper limit of normal
  • Creatinine ≤ 2.0 mg/dL (for adults)
  • Normal renal function (for pediatric patients)
  • Cardiac function normal as measured by MUGA scan or echocardiogram
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for at least 6 months after completion of study treatment
  • HIV negative
  • No active graft-versus-host disease ≥ grade 2
  • No active, uncontrolled infection
  • No fever
  • No unstable CT scans of the lungs, sinuses, or abdomen within the past 4 weeks
  • No arrhythmias (other than atrial flutter or fibrillation) requiring medication
  • No dyspnea at rest or with minimal exertion
  • No uncontrolled congestive heart failure
  • No myocardial infarction within the past 3 months
  • No history of severe coronary artery disease
  • No other significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance or interfere with consent, study participation, follow up, or interpretation of study results

PRIOR CONCURRENT THERAPY:

  • Must have recovered from all acute toxic effects from prior treatment
  • More than 30 days since prior investigational cytotoxic agents
  • At least 3 days since prior azacitidine, thalidomide, hydroxyurea, imatinib mesylate, or interferon
  • At least 1 week since prior growth factors except epoetin alfa
  • More than 3 weeks since any other prior anticancer therapy
  • No concurrent chemotherapy, radiotherapy, or immunotherapy
  • No other concurrent anticancer investigational or commercial agents

  • No routine prophylactic use of a colony-stimulating factor (filgrastim [G-CSF] or sargramostim [GM-CSF])

    • Therapeutic use of colony-stimulating factors may be considered at the discretion of the investigator
  • No prolonged use of corticosteroids to prevent or treat emesis or as a chemotherapeutic agent

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

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

November 1, 2005

Primary Completion (ACTUAL)

April 1, 2010

Study Registration Dates

First Submitted

February 16, 2006

First Submitted That Met QC Criteria

February 16, 2006

First Posted (ESTIMATE)

February 17, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

May 6, 2010

Last Update Submitted That Met QC Criteria

May 5, 2010

Last Verified

May 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J0561 CDR0000456431
  • P30CA006973 (U.S. NIH Grant/Contract)
  • JHOC-J0561
  • JHOC-00000845

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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