Clinical trial NCT01279096: Safety of Clofarabine With Multiagent Chemotherapy in Childhood Acute Lymphoblastic Leukemia
Official title: A Phase I Dose Escalation Study of Clofarabine Given in Combination With Multi-agent Therapy for Remission Induction in Pediatric Patients With Acute Lymphoblastic Leukemia in First Relapse or Refractory to First Line Therapy -
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Lymphoid Leukemia Relapse
Acute Lymphoid Leukemia Relapse After Bone Marrow Transplant
Keywords: Acute lymphoblastic leukemia
relapse
childhood
clofarabine
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Centre Hospitalier Universitaire de Besancon
name: Saint-Louis Hospital, Paris, France
name: Assistance Publique - Hôpitaux de Paris
name: Hospices Civils de Lyon
name: University Hospital, Toulouse
name: Central Hospital, Nancy, France
name: University Hospital, Marseille
name: University Hospital, Bordeaux
name: Nantes University Hospital
name: Rennes University Hospital
First posted: 2011-01-19
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 23
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: maximum tolerated dose of clofarabine in combination with etoposide, asparaginase, mitoxantrone and dexamethasone
timeFrame: within the 40 days after the chemotherapy
Secondary outcomes:
measure: efficacy of clofarabine used in combination with etoposide, asparaginase, mitoxantrone and dexamethasone
timeFrame: 40 days after the chemotherapy
measure: Event free survival
timeFrame: 4 months
Other outcomes:
Locations:
city: Besançon
country: France
facility: Besançon University Hospital
city: Lille
country: France
facility: Lille University Hospital
Study officials:
affiliation: Lille Unıversity Hospital, Lille, France
name: Brigitte Nelken, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Besancon University Hospital
name: Pıerre S Rohrlich, MD, PhD
role: STUDY_CHAIR
References: