Safety of Clofarabine With Multiagent Chemotherapy in Childhood Acute Lymphoblastic Leukemia

NCT ID: NCT01279096

Last Updated: 2014-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2013-06-30

Brief Summary

The purpose of this study is to determine Maximum Tolerated Dosage (MTD), Dosage Limited Toxicities (DLT), and the Rate Phase 2 Dosage of clofarabine when used in combination with etoposide, asparaginase, mitoxantrone and dexamethasone and to assess the feasibility and safety of this combination regimen to treat children with high risk relapsed or refractory acute lymphoblastic leukemia (ALL).

Detailed Description

I.3 Primary Objectives :

To determine the MTD of escalating doses of clofarabine starting from 20 mg/m2/day to 40 mg/m2/day from day 1 to day 5, as a replacement of cytarabine as part of a combination of etoposide, asparaginase, mitoxantrone and dexamethasone (VANDA regimen).

I.4 Secondary Objectives :

1. To determine the safety and tolerability of clofarabine when used in combination with etoposide, asparaginase, mitoxantrone and dexamethasone (VANDA regimen) and determine the duration, seriousness, and relationship of adverse events that occur during the treatment and follow-up periods ; we search DLT

2. To determine the Overall Response rate (OR) (Complete Remission + Complete Remission without platelet's normalization) of clofarabine plus etoposide ,asparaginase, mitoxantrone and dexamethasone (VANDA regimen) in pediatric patients with refractory or relapsed ALL at the established clofarabine RP2D.

3. To document the rate of Partial Response[s] in the study population

4. To document time-to-event parameters, including duration of remission, Event Free Survival (EFS), 4-month EFS, and overall survival (OS).

Conditions

Acute Lymphoid Leukemia Relapse; Acute Lymphoid Leukemia Relapse After Bone Marrow Transplant

Keywords

Acute lymphoblastic leukemia; relapse; childhood; clofarabine

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Clofarabine

escalating doses of clofarabine starting from 20 mg/m2/day to 40 mg/m2/day from day 1 to day 5 used in association with etoposide, asparaginase, mitoxantrone and dexamethasone

Intervention Type: DRUG

Other Intervention Names

etoposide,; asparaginase,; mitoxantrone; dexamethasone

Eligibility Criteria

Inclusion Criteria

• 1 to 21 years old at the date of acute lymphoblastic leukemia initial diagnosis
• Very early medullary first relapse occurring during the first 18th months after complete remission OR patients with second relapse OR a relapse occurring 6 months or more after myeloablative stem cell transplantation will be eligible.
• Have a Karnofsky Performance Status (KPS) of ≥70 for patients >10 years of age or a Lansky Performance Status (LPS) of ≥60 for patients ≤10 years of age.
• No concomitant malignant disease.
• No active uncontrolled infection.
• Have adequate renal and hepatic functions
• absence of concomitant severe cardiovascular disease, i.e. congestive heart failure
• 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

• Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• Use of any investigational agent within 30 days.
• Known hypersensitivity to clofarabine or excipients.
• Known hypersensitivity to mitoxantrone, etoposide or excipients.
• Allergy to both E Coli-Asparaginase and Erwinia Asparaginase
• Prior transplant less than 6 months ago.
• Trisomy 21
• 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.
• 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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 23 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Besancon

OTHER

Sponsor Role: collaborator

Saint-Louis Hospital, Paris, France

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: collaborator

Hospices Civils de Lyon

OTHER

Sponsor Role: collaborator

University Hospital, Toulouse

OTHER

Sponsor Role: collaborator

Central Hospital, Nancy, France

OTHER

Sponsor Role: collaborator

University Hospital, Marseille

OTHER

Sponsor Role: collaborator

University Hospital, Bordeaux

OTHER

Sponsor Role: collaborator

Nantes University Hospital

OTHER

Sponsor Role: collaborator

Rennes University Hospital

OTHER

Sponsor Role: collaborator

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brigitte Nelken, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Lille Unıversity Hospital, Lille, France

Pıerre S Rohrlich, MD, PhD

Role: STUDY_CHAIR

Besancon University Hospital

Locations

Besançon University Hospital

Besançon, , France

Lille University Hospital

Lille, , France

Countries

France

Other Identifiers

2008_40/0905

Identifier Type: OTHER

Identifier Source: secondary_id

2009-010826-20

Identifier Type: -

Identifier Source: org_study_id