A Study of Clofarabine in Japanese Paediatric Patients With Relapsed or Refractory Acute Lymphoblastic Leukaemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT01196013
First received: September 3, 2010
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: Clofarabine
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 ]

Enrollment: 7
Study Start Date: August 2010
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clofarabine Drug: Clofarabine
Intravenous, 30 mg/m2, 52 mg/m2
Other Name: Evoltra, Clolar, JC0707

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed and written informed consent provided by patients ≥ 20 years old or by the parents or guardians of patients less than 20 years old. Investigator should verbally obtain informed assent from the patients 7 years old or older and written informed assent from patients 12 years old or older.
  • Greater than or equal to 25 percent blasts present in the bone marrow and/or peripheral blood count and diagnosed with ALL .at time of enrollment
  • Patients with relapsed or refractory ALL. Patients must not be eligible for therapy of higher clinical benefit potential and must be in second or subsequent relapse and/or refractory, i.e. failed to achieve remission following 2 or more different regimens, or for whom no other therapy with greater potential clinical benefit exists.
  • Have a Karnofsky Performance Status of greater than or equal to 70 for patients 10 years of age or older or Lansky Performance Status greater than or equal to 70 for patients below 10 years of age.
  • Patients whose hepatic, renal, and pancreatic functional tests are within the ranges defined in the protocol.

Exclusion Criteria:

  • Received previous treatment with clofarabine.
  • Have received any other investigational agent within 30 days prior to the first dose of the study drug.
  • Have received any other chemotherapy within 14 days prior to the first dose of clofarabine. However, intrathecal drug administration is allowed up to 24 hours prior to the first dose of clofarabine. In addition, the patient must have been recovered from acute toxicity related to other chemotherapy or investigational agents (baseline or less than or equal to Common Terminology Criteria for Adverse Events ver 3.0 Grade 1)
  • Have systemic fungal, bacterial, viral, or other infection that cannot be controlled(defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). In addition, for patients with a history of fever (≥38.5˚C) within the preceding 3 days at the time of enrollment, documentation of negative blood cultures for at least 48 hours required.
  • Have a psychiatric disorder that would interfere with consent, study participation, or follow-up.
  • Patients whose spinal fluid tested immediately before the study registration within 7 days before dose indicates symptomatic Central Nervous System (CNS) involvement (i.e.CNS3).
  • Have any other severe concurrent disease or a history of serious organ dysfunction or disease involving the heart, kidney, liver, or pancreas.
  • Have received hematopoietic stem cell transplantation (HSCT) within 3 months prior to providing the consent or have acute graft-versus-host disease (GVHD) (greater than or equal to Grade 2) requiring immunosuppressive therapy or severe (systemic) chronic GVHD.
  • Have a prior positive test for Hepatitis B surface (HBs) antigen or antibody, HBc antibody, Hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody. (The patients who have had treatment of vaccine and are positive for HBs antibody are eligible).
  • Are pregnant or nursing. Male and female patients of reproductive potential must agree to use an effective means of birth control to avoid pregnancy during the study period and for 180 days after the last dose of study drug.
  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: NCT01196013

Locations
Japan
National Kyusyu Cancer Center
Fukuoka, Japan
Fukushima Medical University Hospital
Fukushima, Japan
Kagoshima University Medical and Dental Hospital
Kagoshima, Japan
Tokai University Hospital
Kanagawa, Japan
Niigata Cancer Center Hospital
Niigata, Japan
Osaka City General Hospital
Osaka, Japan
Saitama Chilidren's Medical Center
Saitama, Japan
Shizuoka Children's Hospital
Shizuoka, Japan
St. Luke's International Hospital
Tokyo, Japan
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01196013     History of Changes
Other Study ID Numbers: CLO05908
Study First Received: September 3, 2010
Last Updated: March 17, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Clofarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014