A Study of Clofarabine in Japanese Paediatric Patients With Relapsed or Refractory Acute Lymphoblastic Leukaemia
The purpose of this study is primarily to assess the safety, tolerability and pharmacokinetics (PK) of clofarabine intravenously administered to pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) or for whom no other therapy with greater potential clinical benefit exists. The dosing regimen for the intravenous (IV) clofarabine is 30 or 52 mg/m2/day for 5 consecutive days. The secondary objectives are to document the activity of clofarabine and to explore the impact of deoxycytidine kinase (dCK) promoter polymorphism on PK and treatment outcome.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Open-label, Multi-center Study of Clofarabine in Japanese Paediatric Patients With Relapsed or Refractory Acute Lymphoblastic Leukaemia|
- Maximum Tolerated Dose (MTD) [ Time Frame: 14 days (1st cycle) ] [ Designated as safety issue: Yes ]
- Safety as evaluated by adverse events (incidence, severity, duration, causality, seriousness, type) [ Time Frame: 45 days after final study drug administration ] [ Designated as safety issue: Yes ]
- Pharmacokinetics as measured by maximum drug serum concentration (Cmax) [ Time Frame: Day 1 to Day 5 ] [ Designated as safety issue: No ]
- Pharmacokinetics as measured by Time to maximum serum concentration (Tmax) [ Time Frame: Day 1 to Day 5 ] [ Designated as safety issue: No ]
- Pharmacokinetics as measured by Area Under the drug-concentration curve (AUC) [ Time Frame: Day 1 to Day 5 ] [ Designated as safety issue: No ]
- Pharmacokinetics as measured by half life (t1/2) [ Time Frame: Day 1 to Day 5 ] [ Designated as safety issue: No ]
- Pharmacokinetics as measured by renal clearance (CLr) [ Time Frame: Day 1 to Day 5 ] [ Designated as safety issue: No ]
|Study Start Date:||August 2010|
|Study Completion Date:||May 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Intravenous, 30 mg/m2, 52 mg/m2
Other Name: Evoltra, Clolar, JC0707
This is a Phase I Study of Clofarabine in Japanese Paediatric Patients With Relapsed or Refractory Acute Lymphoblastic Leukaemia.
Subjects will receive intravenous administration of clofarabine at 30 or 52 mg/m2/day (2 hours) for 5 consecutive days and then the administration will be withheld until Day 14. If there is no evidence of recovery in neutrophil (≥750/mm3) and/or platelet count (≥50,000/mm3), the therapy may be withheld up to Day 42. However, in the absence of progression based on the judgment of the investigator after each cycle of treatment and the benefit of continued treatment is judged to exceed the risk, subjects may receive up to a total of six cycles. If a subject is receiving two or more cycles, a written consent must be obtained prior to start of Cycle 2.
When a subject completes the final dose, the safety will be observed and followed-up for 45 days after the final study drug administration.
Cohort 1 will receive 30 mg/m2/day x 5 days at Cycle 1 and will be assessed for tolerability. Samples will be drawn to assess pharmacokinetics at this dose. If subjects do not develop adverse events indicative of dose limiting toxicity (DLT) at Cycle 1, the dose will be increased to 52 mg/m2/day x 5 days from Cycle 2 and the subjects will be assessed for safety and activity only.
Cohort 2 will receive 52 mg/m2/day x 5 days at Cycle 1 and will be assessed for the tolerability. Samples will be drawn to assess pharmacokinetics at this dose.
Whether or not proceeding to Cohort 2 after the Cycle 1 of Cohort 1 is completed will be determined by the sponsor based on the assessment of the safety data and the recommendation of the Data Safety Monitoring Board (DSMB).
|National Kyusyu Cancer Center|
|Fukushima Medical University Hospital|
|Kagoshima University Medical and Dental Hospital|
|Tokai University Hospital|
|Niigata Cancer Center Hospital|
|Osaka City General Hospital|
|Saitama Chilidren's Medical Center|
|Shizuoka Children's Hospital|
|St. Luke's International Hospital|
|Study Director:||Medical Monitor||Genzyme, a Sanofi Company|