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

Sponsors and Collaborators:	University of Nebraska National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00503880

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	Drug: clofarabine Drug: cytarabine Drug: filgrastim Procedure: biopsy Procedure: gene expression profiling	Phase I Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Filgrastim Cytarabine Cytarabine hydrochloride Granulocyte colony-stimulating factor Clofarabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of clofarabine (phase I) [ Designated as safety issue: Yes ]
Presence of hematologic response (phase II) [ Designated as safety issue: No ]

Estimated Enrollment:	33
Study Start Date:	May 2007
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

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

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

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Lori J. Maness, MD

University of Nebraska

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	UNMC Eppley Cancer Center at the University of Nebraska Medical Center ( Lori J. Maness )
Study ID Numbers:	CDR0000555504, UNMC-03207, UNMC 032-07
Study First Received:	July 17, 2007
Last Updated:	December 27, 2008
ClinicalTrials.gov Identifier:	NCT00503880
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

Study placed in the following topic categories:

Clofarabine
Myelodysplastic syndromes
Preleukemia
Precancerous Conditions
Hematologic Diseases
Myelodysplasia

Myelodysplastic Syndromes
Neoplasm Metastasis
Bone Marrow Diseases
Aggression
Cytarabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Disease
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs

Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Pathologic Processes
Syndrome
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009