Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00293410
First received: February 16, 2006
Last updated: May 5, 2010
Last verified: May 2010
  Purpose

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.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Myelodysplastic/Myeloproliferative Diseases
Drug: clofarabine
Drug: cyclophosphamide
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Adults and Children With Relapsed or Refractory Acute Leukemias

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Estimated Enrollment: 70
Study Start Date: November 2005
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00293410

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Judith E. Karp, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00293410     History of Changes
Other Study ID Numbers: J0561 CDR0000456431, P30CA006973, JHOC-J0561, JHOC-00000845
Study First Received: February 16, 2006
Last Updated: May 5, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
childhood acute erythroleukemia (M6)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
accelerated phase chronic myelogenous leukemia
chronic idiopathic myelofibrosis
chronic myelomonocytic leukemia
juvenile myelomonocytic leukemia
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
acute undifferentiated leukemia
blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
adult acute basophilic leukemia
adult acute eosinophilic leukemia
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)

Additional relevant MeSH terms:
Disease
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Clofarabine
Cyclophosphamide
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014