A Study of Oral Clofarabine in Adult Patients With Myelodysplastic Syndromes (MDS)

A Phase I, Open-Label, Dose-Finding and Food Effect Study of Oral Clofarabine in Previously Treated Adult Patients With Myelodysplastic Syndromes (MDS)

This study will be used to determine the maximum tolerated dose of oral clofarabine when administered daily for 14 consecutive days repeated every 21 days.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: clofarabine; Drug: clofarabine

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States
      • Malignant Hematology Administration, H. Lee Moffitt Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States
      • Division of Hematology Mayo Clinic
  • Texas
    • San Antonio, Texas, United States
      • Cancer Care Centers of South Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provide signed, written informed consent.
• Be at least 18 years old.
• Have a pathologically confirmed MDS and score according to the IPSS at study entry. Pathologic confirmation is the responsibility of the investigator.
• Have been treated previously for MDS as follow: a.Patients must have had at least 1, but no more than 2, prior treatment regimens; b.Patients must not have refractory (i.e., disease progression or no evidence of response while on treatment) to more than 1 prior treatment regimen.
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Be able to comply with study procedures and follow-up examinations.
• Have adequate hepatic and renal function.
• Be non-fertile or agree to use birth control during the study through the end of the last treatment visit and at least 90 days after.

Exclusion Criteria:

• Have had a readjustment of dose and/or schedule of erythropoietin, granulocyte colony stimulating factor(G-CSF) or other growth factors within 8 weeks prior to the first dose of oral clofarabine.
• Have had any other chemotherapy or any investigational therapy for MDS within 4 weeks of the first dose of oral clofarabine.
• Have not recovered to ≤ Grade 2 in severity of any drug-related non-hematologic toxicity prior to the first dose of oral clofarabine.
• Have an uncontrolled systemic fungal, bacterial, viral or other infection. Have a history of serious disease involving the heart.
• Have a clinically significant cardiac assessment at screening or a known family history QT prolongation.
• Currently uses a medication known to prolong the QT interval.
• Have had any prior treatment with clofarabine (IV or oral).
• Have had a diagnosis of another malignancy, unless the patient has been disease free for at least 3 years after completing curative intent therapy except for the following: a. 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 or the condition has been completed. b. 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 (HIV).
• Have gastrointestinal disease or prior surgery, which may affect the ability of the patient to absorb oral clofarabine.
• Is currently participating in another concurrent investigational protocol that is not restricted to data and/or sample collection for patient demographic and/or disease purposes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; clofarabine Dose Escalation	Drug: clofarabine; Drug given Daily x 14 days and 7 days of rest for 21 day cycle; Drug: clofarabine; Drug given Daily X 14 days and 7 days of rest for 21 day cycle
Experimental: Part B; Part B is an open-label, replicated cross-over study in which 12 additional patients will be enrolled and treated at the MTD determined in part A to evaluate the effect of food on the PK disposition of oral clofarabine.	Drug: clofarabine; Drug given Daily x 14 days and 7 days of rest for 21 day cycle; Drug: clofarabine; Drug given Daily X 14 days and 7 days of rest for 21 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated dose levels	First Cycle

Secondary Outcome Measures

Outcome Measure	Time Frame
PK profile	After MTD is established
Food effect on profile	After MTD is established
Activity of clofarabine in this dosing regimen	Duration of Study

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: September 9, 2008
• First Submitted That Met QC Criteria: September 9, 2008
• First Posted (Estimate): September 10, 2008

Study Record Updates

• Last Update Posted (Estimate): May 21, 2015
• Last Update Submitted That Met QC Criteria: May 19, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Myelodysplastic; Oral Clofarabine,; relapsed/refractory MDS,
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Clofarabine
• Other Study ID Numbers: CLOMDS01206