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

This study has been completed.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01003678
First received: October 27, 2009
Last updated: May 8, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Clofarabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study Evaluating the Safety and Tolerability of Oral Clofarabine in Intermediate to High Risk Myelodysplastic Patients

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • To determine the safety, maximum tolerated dose (MTD) and recommended phase II dose of Clofarabine in patients with myelodysplastic syndrome (MDS). [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the efficacy of Clofarabine in patients with MDS [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • To determine the differences in clofarabine triphosphate levels in cells following clofarabine treatment [ Time Frame: Pre, Day 1: Hourly for 6 hours, Pre Day 5:Hourly for 5 hours ] [ Designated as safety issue: No ]
  • Determine the differences in clofarabine plasma levels following clofarabine treatment [ Time Frame: Pre, Day 1: Hourly for 6 hours, Pre Day 5:Hourly for 5 hours ] [ Designated as safety issue: No ]
  • Evaluate the effect of clofarabine on DNA methylation [ Time Frame: Pre and Day 1 ] [ Designated as safety issue: No ]
  • Estimate post-treatment p53R2levels in patients treated at the MTD (in the expanded cohort) [ Time Frame: At 6 months ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: October 2009
Study Completion Date: October 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Level 1
1 mg daily for 5 consecutive days followed by 23 days off drug
Drug: Clofarabine

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.


Detailed Description:

The specific purpose of the study is to determine the safety, maximum tolerated dose (MTD) and recommended Phase II dose of clofarabine in patients with MDS.

  • We will start at a dose of 1 mg daily.
  • We will treat a group of 3 patients with clofarabine at that dose level.
  • If there are no severe side effects seen at that dose level, then the next group of 3 patients will receive a higher dose.
  • Treatment of groups of 3 patients will continue at higher dose levels until severe side-effects are noted.
  • If more than 1 of the 3 patients experiences a severe side effect, dosing will be stopped at that level.
  • If only one of the three patients experience a severe side effect, then three more patients will be treated, at that dose level and if they too experience severe side effects, then dose escalation will be stopped and the maximum tolerated dose will be determined.
  • 10 more patients will be enrolled at the maximum tolerated dose.
  • There will be up to 5 dose levels tested.
  • We plan to test how much of the drugs are in the patient's blood at different times, and the levels of certain proteins in their blood.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01003678

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Roswell Park Cancer Institute
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Wetzler Meir, MD Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01003678     History of Changes
Other Study ID Numbers: I 144208
Study First Received: October 27, 2009
Last Updated: May 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Roswell Park Cancer Institute:
Myelodysplastic syndrome
Clofarabine
low-dose oral clofarabine
intermediate risk Myelodysplastic syndrome
high risk Myelodysplastic syndrome

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes
Clofarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 16, 2014