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

NCT00503880 | Terminated Phase 1 Results

• 2 other identifiers: 0032-07-FBP30CA036727
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Myelodysplastic Syndromes

Keywords

de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

• Assess Quality of Life

  7 months

• Time to Acute Myelooid Leukemia Transformation or Death.

  7months

• Cytogenetic Response Rates

  7 months

• Changes in Flow of Cytometric Patterns.

  7 months

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Biological: filgrastim; Drug: clofarabine; Drug: cytarabine; Genetic: microarray analysis; Procedure: biopsy

Interventions

filgrastim BIOLOGICAL

subcutaneously one day prior to treatment

Also known as: Neupogen

Treatment

clofarabine DRUG

single IV dose over 1 hour daily for 5 days

Also known as: Clolar

Treatment

cytarabine DRUG

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

Also known as: cytosine arabinoside

Treatment

microarray analysis GENETIC

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

Treatment

biopsy PROCEDURE

bone marrow biopsy

Treatment

Eligibility Criteria

• Age: 19 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Filgrastim; Clofarabine; Cytarabine; Microarray Analysis; Biopsy

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Microchip Analytical Procedures; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Results Point of Contact

• Title: Lori Maness-Harris, MD
• Organization: University of Nebraska Medical Center

lmaness@unmc.edu

402-559-3848

Study Officials

• Lori J Maness, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2007
• First Posted: July 19, 2007
• Study Start: May 7, 2007
• Primary Completion: October 13, 2009
• Study Completion: October 13, 2009
• Last Updated: September 18, 2023
• Results First Posted: April 13, 2018

Record last verified: 2023-08

Locations

US (1)