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

NCT01196013 | Completed Phase 1 DMC

• 1 other identifier: CLO05908
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (7)

• Maximum Tolerated Dose (MTD)

  14 days (1st cycle)

• Safety as evaluated by adverse events (incidence, severity, duration, causality, seriousness, type)

  45 days after final study drug administration

• Pharmacokinetics as measured by maximum drug serum concentration (Cmax)

  Day 1 to Day 5

• Pharmacokinetics as measured by Time to maximum serum concentration (Tmax)

  Day 1 to Day 5

• Pharmacokinetics as measured by Area Under the drug-concentration curve (AUC)

  Day 1 to Day 5

• Pharmacokinetics as measured by half life (t1/2)

  Day 1 to Day 5

• Pharmacokinetics as measured by renal clearance (CLr)

  Day 1 to Day 5

Study Arms (1)

Clofarabine

EXPERIMENTAL

Drug: Clofarabine

Interventions

Clofarabine DRUG

Intravenous, 30 mg/m2, 52 mg/m2

Also known as: Evoltra, Clolar, JC0707

Clofarabine

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (9)

National Kyusyu Cancer Center

Fukuoka, Japan

Location

Fukushima Medical University Hospital

Fukushima, Japan

Location

Kagoshima University Medical and Dental Hospital

Kagoshima, Japan

Location

Tokai University Hospital

Kanagawa, Japan

Location

Niigata Cancer Center Hospital

Niigata, Japan

Location

Osaka City General Hospital

Osaka, Japan

Location

Saitama Chilidren's Medical Center

Saitama, Japan

Location

Shizuoka Children's Hospital

Shizuoka, Japan

Location

St. Luke's International Hospital

Tokyo, Japan

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Clofarabine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2010
• First Posted: September 8, 2010
• Study Start: August 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: March 19, 2014

Record last verified: 2014-03

Locations

JP (9)