Safety and Tolerability of Oral Clofarabine in Intermediate to High Risk Myelodysplastic Patients

NCT01003678 | Terminated Phase 1 DMC

• 1 other identifier: I 144208
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I trial for patients with intermediate or high risk myelodysplastic syndrome (MDS). The study agent, clofarabine, is produced by Genzyme Pharmaceuticals.

Conditions

Myelodysplastic Syndrome

Keywords

Myelodysplastic syndrome; Clofarabine; low-dose oral clofarabine; intermediate risk Myelodysplastic syndrome; high risk Myelodysplastic syndrome

Outcome Measures

Primary Outcomes (1)

• To determine the safety, maximum tolerated dose (MTD) and recommended phase II dose of Clofarabine in patients with myelodysplastic syndrome (MDS).

  Up to 6 months

Secondary Outcomes (5)

• To determine the efficacy of Clofarabine in patients with MDS

  Up to 6 months

• To determine the differences in clofarabine triphosphate levels in cells following clofarabine treatment

  Pre, Day 1: Hourly for 6 hours, Pre Day 5:Hourly for 5 hours

• Determine the differences in clofarabine plasma levels following clofarabine treatment

  Pre, Day 1: Hourly for 6 hours, Pre Day 5:Hourly for 5 hours

• Evaluate the effect of clofarabine on DNA methylation

  Pre and Day 1

• Estimate post-treatment p53R2levels in patients treated at the MTD (in the expanded cohort)

  At 6 months

Study Arms (1)

Level 1

EXPERIMENTAL

1 mg daily for 5 consecutive days followed by 23 days off drug

Drug: Clofarabine

Interventions

Clofarabine DRUG

Dose Escalation Schedule - Level 1: 1 mg daily x 5 days (orally) followed by 23 days off drug. Levels 2, 3, 4 and 5 are: 3, 5, 10 and 15 mg daily x 5 days followed by 23 days off drug.

Level 1

Eligibility Criteria

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

You may qualify if:

• Provide signed written informed consent.
• Patients with MDS must have IPSS score that falls in the intermediate or high risk disease (intermediate 1 will have to be transfusion dependent).
• Patients may have received up to two prior therapies for MDS including one hypomethylating agent and/or a biologic agent (biologic agents include GM-CSF or equivalent, danazol or equivalent, Sunitinib, Revlimid, ATG, or a vaccine).
• Age ≥ 18
• Have adequate renal and hepatic functions as indicated by the following laboratory values:
• Serum creatinine ≤ 1 mg/dL; if serum creatinine \>l mg/dL, then the estimated glomerular filtration rate (GFR) must be \>50 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation.
• Serum bilirubin ≤1.5 mg/dL x upper limit of normal (ULN)
• Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 x ULN
• Alkaline phosphatase ≤2.5 x ULN
• Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
• Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
• Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

You may not qualify if:

• Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
• Active CNS disease
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Pregnant or lactating patients.
• Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
• Have had any prior treatment with clofarabine
• Have had a diagnosis of another malignancy, unless the patient has been disease free for at least 3 years following the completion of curative intent therapy, with the following exceptions:
• Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed.
• Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed.
• Have prior positive test for the Human Immunodeficiency Virus (HN).
• Have prior positive test for the Human Immunodeficiency Virus (HN).
• Have currently active gastrointestinal disease, or prior surgery that may affect the ability of the patient to absorb oral clofarabine.
• Patients taking proton pump inhibitors such as omeprazole (Prilosec®), lansoprazole (Prevacid®), or esomeprazole (Nexium®). Those who cannot stop taking these drugs should be switched to H2 blockers such as famotidine (Pepcid®)or ranitidine (Zantac®).
• Patients taking alternative medicines (such as herbal or botanical) are not permitted.

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Clofarabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Study Officials

• Wetzler Meir, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

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: October 27, 2009
• First Posted: October 29, 2009
• Study Start: October 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: October 1, 2013
• Last Updated: June 3, 2016

Record last verified: 2016-06

Locations

US (1)