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

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00503880
• Other study ID #: 0032-07-FB
• Secondary ID: P30CA036727
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 7, 2007
• Est. completion date: October 13, 2009

Study information

• Verified date: August 2023
• Source: University of Nebraska
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: October 13, 2009
• Est. primary completion date: October 13, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Biological:
• filgrastim
subcutaneously one day prior to treatment

Drug:
• clofarabine
single IV dose over 1 hour daily for 5 days
• 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

Locations

Country	Name	City	State
United States	University of Nebraska Medical Center	Omaha	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
University of Nebraska	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose of Clofarabine (Phase I)	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).	7 months
Primary	Presence of Hematologic Response (Phase II)	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.	Following phase I, responses must last at least 8 weeks.
Secondary	Assess Quality of Life	To assess effects on quality of life of this patient population (questionnaire).	7 months
Secondary	Time to Acute Myelooid Leukemia Transformation or Death.	To assess the time to acute myeloid leukemia transformation or death.	7months
Secondary	Cytogenetic Response Rates	To assess cytogenetic response rates.	7 months
Secondary	Changes in Flow of Cytometric Patterns.	To assess changes in flow cytometric patterns.	7 months