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

NCT ID: NCT00503880

Last Updated: 2023-09-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-07
• Study Completion Date: 2009-10-13

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.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

G-CSF 300 μg subcutaneously to begin one day prior to treatment and continued until ANC greater than 1.0 or recovers back to the patients baseline ANC for 3 days in a row subsequent to completion of chemotherapy (SOC) Low-dose Cytarabine 10 mg/m2 subcutaneously daily starting on day 1 for the first 5 consecutive days of the treatment course 2-4 hours following the end of the clofarabine infusion. (SOC) Clofarabine starting at dose level 0. Dose-10 mg/m2 IV over 1 hour daily starting on day 1 for the first 5 consecutive days of the treatment course The G-CSF and cytarabine doses are fixed. The dose of clofarabine is initially fixed. For the subsequent cohort, the dose of clofarabine will be advanced to the next dose level.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

subcutaneously one day prior to treatment

clofarabine

Intervention Type: DRUG

single IV dose over 1 hour daily for 5 days

cytarabine

Intervention Type: DRUG

subcutaneously daily for 5 days 2-4 hours following the end of the Clofarabine infusion

microarray analysis

Intervention Type: GENETIC

Both standard cytogenetic testing and FISH (fluorescent in situ hybridization) are adequate to assess responses.

biopsy

Intervention Type: PROCEDURE

bone marrow biopsy

Interventions

filgrastim

subcutaneously one day prior to treatment

Intervention Type: BIOLOGICAL

clofarabine

single IV dose over 1 hour daily for 5 days

Intervention Type: DRUG

cytarabine

subcutaneously daily for 5 days 2-4 hours following the end of the Clofarabine infusion

Intervention Type: DRUG

microarray analysis

Both standard cytogenetic testing and FISH (fluorescent in situ hybridization) are adequate to assess responses.

Intervention Type: GENETIC

biopsy

bone marrow biopsy

Intervention Type: PROCEDURE

Other Intervention Names

Neupogen; Clolar; cytosine arabinoside

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lori J Maness, MD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska Medical Center

Omaha, Nebraska, United States

Countries

United States

Other Identifiers

P30CA036727

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0032-07-FB

Identifier Type: -

Identifier Source: org_study_id