Clofarabine, Cytarabine, and G-CSF in Treating Patients With Myelodysplastic Syndromes

This study has been terminated.
(Funding)
Sponsor:
Collaborator:
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00503880
First received: July 17, 2007
Last updated: February 3, 2011
Last verified: February 2011
  Purpose

RATIONALE: Drugs used in chemotherapy, such as clofarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or in peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving clofarabine and cytarabine together with G-CSF may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works when given together with cytarabine and G-CSF in treating patients with myelodysplastic syndromes.


Condition Intervention Phase
Myelodysplastic Syndromes
Biological: filgrastim
Drug: clofarabine
Drug: cytarabine
Genetic: microarray analysis
Procedure: biopsy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose Escalation Phase I/II Study of Clofarabine Plus Cytarabine With Growth Factor Priming in Patients Who Are Not Felt to be Candidates for More Aggressive Treatment, With Int-2 and High-Risk MDS

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Maximum tolerated dose of clofarabine (phase I) [ Time Frame: When/if 2 out of 6 patients experience dose limiting toxicity (DLT based on NCI CTC version 2 grading criteria) ] [ Designated as safety issue: Yes ]
    Maximum Tolerated Dose (MTD) is defined to be the dose cohort below which 2 out of 6 patients experience dose limiting toxicities or the highest dose cohort, if 2 limiting toxicities are not observed at any dose cohort. These will be presented as actual rates. Dose limiting toxicity (DLT) will be defined according to oncology standards based on NCI CTC version 2 grading criteria (DLT = > grade 3 non-hematological toxicity or any > 4 hematological toxicity that persists for more than 4 weeks and in the opinion of the investigator is felt not to be due to disease).

  • Presence of hematologic response (phase II) [ Time Frame: Following phase I, responses must last at least 8 weeks. ] [ Designated as safety issue: No ]

    These are measured in patients with pretreatment abnormalities defined as:

    Hemoglobin < 11 g/dL or transfusion dependence [erythroid- E] Platelets less than 100 x 109/L or platelet-transfusion dependence [platelet- P] Absolute neutrophil count (ANC) less than 1.0 x 109/L [neutrophil- N] Pretreatment baseline measures of cytopenias are averages of at least 2 measurements (not influenced by transfusions)- at least 1 week apart.



Estimated Enrollment: 33
Study Start Date: May 2007
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: filgrastim
    subcutaneously one day prior to treatment
    Drug: clofarabine
    single IV dose over 1 hour daily for 5 days
    Drug: cytarabine
    subcutaneously daily for 5 days 2-4 hours following the end of the Clofarabine infusion
    Genetic: microarray analysis
    Both standard cytogenetic testing and FISH (fluorescent in situ hybridization) are adequate to assess responses.
    Procedure: biopsy
    bone marrow biopsy
Detailed Description:

OBJECTIVES:

Primary

  • To determine the maximum tolerated dose (MTD) of clofarabine when administered with low-dose cytarabine and filgrastim (G-CSF) in patients with intermediate-2 or high-risk myelodysplastic syndromes (MDS).
  • To evaluate efficacy as measured by hematologic response rates in patients who are treated with this novel combination of drugs and who are not candidates for more intensive treatment for intermediate-2 and high-risk MDS.

Secondary

  • To assess effects on quality of life of this patient population.
  • To assess the time to acute myeloid leukemia transformation or death.
  • To assess cytogenetic response rates.
  • To assess changes in flow cytometric patterns.

OUTLINE: This is a phase I, nonrandomized, dose-escalation study of clofarabine followed by a phase II study.

  • Phase I: Patients receive clofarabine IV over 1 hour and low-dose cytarabine subcutaneously (SC) on days 1-5. Patients also receive filgrastim (G-CSF) SC beginning 1 day prior to the start of chemotherapy and continuing through completion of chemotherapy until blood counts recover. Treatment repeats every 6 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of clofarabine 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.

  • Phase II: Patients receive clofarabine at the MTD, cytarabine, and G-CSF as in phase I.

Quality of life is assessed at baseline, prior to course 4, and after completion of study therapy.

Patients undergo bone marrow biopsy at baseline and prior to courses 3, 6, and 8 for evaluation of treatment response. Bone marrow samples are analyzed for myeloblast phenotypic expression profiles, which include the following parameters: percentage of CD34-positive myeloblasts; antigen expression density of CD13, CD34, CD45, and CD117; and aberrant myeloblast expression of CD4, CD11c, CD15, and CD56.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Confirmed pathologic diagnosis of myelodysplastic syndromes
  • International Prognostic Scoring System score of intermediate-2 or high-risk
  • Failed or progressed after 1 prior FDA-approved treatment for MDS OR refused the FDA-approved treatment
  • Not a candidate for intensive or standard chemotherapy or stem cell transplantation, as determined by the treating physician

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST or ALT ≤ 3 times ULN
  • Creatinine < 2.0 mg/dL
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No comorbidity or condition that, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol or that would decrease life expectancy to < 3 months
  • No active, serious infection not controlled by oral or IV antibiotics

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  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: NCT00503880

Locations
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Lori J. Maness, MD University of Nebraska
  More Information

No publications provided

Responsible Party: Lori J. Maness, UNMC Eppley Cancer Center at the University of Nebraska Medical Center
ClinicalTrials.gov Identifier: NCT00503880     History of Changes
Other Study ID Numbers: 032-07, P30CA036727, UNMC-03207, UNMC 032-07
Study First Received: July 17, 2007
Last Updated: February 3, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Nebraska:
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes
Cytarabine
Clofarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014