Safety of Clofarabine With Multiagent Chemotherapy in Childhood Acute Lymphoblastic Leukemia (Vandevol)

University Hospital, Lille

Status and phase

Completed

Phase 1

Conditions

Acute Lymphoid Leukemia Relapse

Acute Lymphoid Leukemia Relapse After Bone Marrow Transplant

Treatments

Drug: Clofarabine

Study type

Interventional

Funder types

Other

Identifiers

NCT01279096

2008_40/0905 (Other Identifier)

2009-010826-20

Details and patient eligibility

About

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).

Full 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 :

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
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.
To document the rate of Partial Response[s] in the study population
To document time-to-event parameters, including duration of remission, Event Free Survival (EFS), 4-month EFS, and overall survival (OS).

Enrollment

20 patients

Sex

All

Ages

1 to 23 years old

Volunteers

No Healthy Volunteers

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.