A Dose Confirmation Study of Oral Clofarabine for Adult Patients Previously Treated for Myelodysplastic Syndromes (MDS)
This study has been completed.
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
First received: September 14, 2007
Last updated: March 17, 2014
Last verified: March 2014
There is no well accepted standard care for patients who fail or are intolerant to any of the currently approved therapies for Myelodysplastic Syndromes (MDS). In this study, patients will be assigned to receive 25mg of oral clofarabine daily for 5 days. Patients may receive up to 8 cycles of treatment with clofarabine as long as the patient continues to benefit and in the absence of progressive disease.
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase IIa Open-label, Dose Confirmation Study of Oral Clofarabine in Adult Patients Previously Treated for Myelodysplastic Syndromes(MDS)
Primary Outcome Measures:
- Maximum Tolerated dose of oral clofarabine (dosed daily x 5) for treatment of previously treated adult patients with MDS or secondary acute myeloid leukemia (following a history of MDS). [ Time Frame: Toxicity observed in first cycle after treatment will be used to confirm an appropriate dose ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- The rate of febrile neutropenia and the toxicity profile for each dose under study. [ Time Frame: duration of the study ] [ Designated as safety issue: No ]
- Efficacy parameters: hematologic improvement(HI);overall response rate/duration (CR,marrow CR,PR,or HI); overall remission rate (CR,marrow CR,or PR);time to AML transformation; overall survival (OS) [ Time Frame: Patients are expected to achieve response during the first 4 cycles of treatment ] [ Designated as safety issue: No ]
- Clofarabine pharmacokinetics (PK) after oral administration [ Time Frame: day 1 of cycle 1 ] [ Designated as safety issue: No ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||March 2011 (Final data collection date for primary outcome measure)
Experimental: clofarabine 25 mg/day
Oral daily x 5 every 28 days. 25 mg/day. Up to 8 cycles
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Have a pathologically confirmed secondary Acute Myeloid Leukemia (following a history of MDS) or MDS with an intermediate 1 (with marrow blasts great than or equal to 5%) intermediate 2 or high risk score as assessed by the International Prognostic Scoring System (IPSS) at study, entry. Patients with refractory anemia with excess blasts in transformation (RAEB-t) recognized by the French-American-British (FAB) system, and chronic myelomonocytic leukemia (CMML) will be allowed into the study. Pathologic confirmation is the responsibility of the site investigator.
- Have previously treated MDS defined as follows: a.)Patients must have had at least one, but no more than two, prior treatment regimens [A treatment regimen is defined as any drug or drug combination administered for treatment of MDS with the intent of inducing at least hematologic improvement (consistent with International Working Group [IWG] criteria); Inadequate treatment, due to drug intolerance or other factors, will still be considered a prior treatment regimen. Hematopoietic growth factors, hydroxyurea, anti-thymocyte globulin (ATG), or supportive care measures (e.g., blood transfusions, immunosuppressive agents, antibiotics) will not be considered treatment regimens for the purpose of study entry.] b.)One of the treatment regimens must have been either 5-azacytidine or decitabine. If 5-azacytidine or decitabine is given as a treatment regimen more than once, it will be considered as 2 different treatment regimens. c.)Patients must not have been refractory (i.e., progression of disease, or no evidence of response, while on the treatment) to more than one prior treatment regimen (to be considered refractory to decitabine or 5-azacitidine, patients must have received greater than or equal to 4 cycles).
- Have documentation of prior transfusion requirements for the preceding 8 weeks (8 weeks prior to first dose of study drug).
- Have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Be able to comply with study procedures and follow-up examinations.
- Have adequate renal and hepatic functions as indicated by predefined laboratory values: a.)Total bilirubin < 1.5 x institutional Upper Limit of Normal (ULN) except for unconjugated hyperbilirubin secondary to treatment for MDS or Gilbert's syndrome; and b.)Aspartate aminotransferase(AST) and Alanine aminotransferase(ALT) < 2.5 x ULN; and c.)Serum creatine < 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >30 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation.
- Be non-fertile or agree to use birth control during the study through the end of last treatment visit and at least 90 days after.
- Have had an adjustment 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 prior therapy for treatment of sAML. Hydroxyurea must not have been received within 24 hours prior to first dose of study drug.
- Have had any other chemotherapy or any investigational therapy within four weeks of first dose of study drug.
- Have had any prior pelvic radiotherapy.
- Have had a prior hematopoietic stem cell transplant for MDS.
- Have not recovered to < grade 2 from any drug-related non-hematologic toxicity prior to first dose of the study drug.
- Have an uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
- Have a psychiatric disorder that would interfere with consent, study participation, or follow-up.
- Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, or liver, in particular: a.)New York Heart Association (NHA) classification stage II, III, or IV congestive heart failure; b.)Coronary artery disease or arteriosclerotic cardiovascular disease (angina, myocardial infraction) within 3 months of first dose of study drug; c.)Any other primary cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
- Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart 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: 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 for 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 currently active gastrointestinal disease, or prior surgery that may affect the ability of the patient to absorb oral clofarabine.
- Participating in other concurrent investigational protocols that are not restricted to data and/or sample collection for patient demographic and/or sample collection for patient demographic and/or disease purposes.
- Have had prior treatment with a known nephrotoxic drug within 2 weeks of the first dose of study drug, unless the patient has a calculated GFR >30 at 2 time points no less than 7 days apart during the 2-week period prior to the first dose of study drug.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00531232
|The University of Chicago
|Chicago, Illinois, United States, 60637 |
|Weill Medical College of Cornell University
|New York, New York, United States, 10065 |
|Wake Forest University Baptist Medical Center
|Winston-Salem, North Carolina, United States, 27157 |
|Cleveland, Ohio, United States, 44195 |
|Baylor University Medical Center Blood Marrow Transplantation Research
|Dallas, Texas, United States, 75246 |
|University of Texas MD Anderson Cancer Center
|Houston, Texas, United States, 77030 |
Genzyme, a Sanofi Company
||Genzyme, a Sanofi Company
No publications provided
||Sanofi ( Genzyme, a Sanofi Company )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||September 14, 2007
||March 17, 2014
||United States: Food and Drug Administration
Keywords provided by Sanofi:
Previously treated Myelodysplastic Syndromes (MDS)
Intermediate-1, Intermediate-2 and High Risk Myelodysplastic Syndromes (MDS)
secondary AML (with history of MDS)
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on August 28, 2014
Bone Marrow Diseases
Molecular Mechanisms of Pharmacological Action