Clinical trial NCT00503880: Clofarabine, Cytarabine, and G-CSF in Treating Patients With Myelodysplastic Syndromes
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-07-19
Enrollment: 2
Sex: ALL
Minimum age (years): 19
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 criteria: Inclusion Criteria:

* Confirmed pathologic diagnosis of myelodysplastic syndromes
* International Prognostic Scoring System score of intermediate-2 or high-riskFailed 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
* 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
* Fertile patients must use effective contraception

Exclusion Criteria:

* Not pregnant or nursing
* 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

Primary outcomes:
measure: Maximum Tolerated Dose of Clofarabine (Phase I)
timeFrame: 7 months
measure: Presence of Hematologic Response (Phase II)
timeFrame: Following phase I, responses must last at least 8 weeks.
Secondary outcomes:
measure: Assess Quality of Life
timeFrame: 7 months
measure: Time to Acute Myelooid Leukemia Transformation or Death.
timeFrame: 7months
measure: Cytogenetic Response Rates
timeFrame: 7 months
measure: Changes in Flow of Cytometric Patterns.
timeFrame: 7 months
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Lori J Maness, MD
role: PRINCIPAL_INVESTIGATOR
References: