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

This study has been completed.
Sponsor:
Collaborators:
Centre Hospitalier Universitaire de Besancon
Saint-Louis Hospital, Paris, France
Assistance Publique - Hôpitaux de Paris
Hospices Civils de Lyon
University Hospital, Toulouse
Central Hospital, Nancy, France
University Hospital, Marseille
University Hospital, Bordeaux
Nantes University Hospital
Rennes University Hospital
Information provided by (Responsible Party):
Brigitte NELKEN, University Hospital, Lille
ClinicalTrials.gov Identifier:
NCT01279096
First received: January 17, 2011
Last updated: July 30, 2013
Last verified: July 2013
  Purpose

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).


Condition Intervention Phase
Acute Lymphoid Leukemia Relapse
Acute Lymphoid Leukemia Relapse After Bone Marrow Transplant
Drug: Clofarabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 -

Resource links provided by NLM:


Further study details as provided by University Hospital, Lille:

Primary Outcome Measures:
  • maximum tolerated dose of clofarabine in combination with etoposide, asparaginase, mitoxantrone and dexamethasone [ Time Frame: within the 40 days after the chemotherapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • efficacy of clofarabine used in combination with etoposide, asparaginase, mitoxantrone and dexamethasone [ Time Frame: 40 days after the chemotherapy ] [ Designated as safety issue: No ]
    Complete remission rate and minimal residual disease level

  • Event free survival [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: January 2010
Study Completion Date: June 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 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
    Other Names:
    • etoposide,
    • asparaginase,
    • mitoxantrone
    • dexamethasone
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

Ages Eligible for Study:   1 Year to 23 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01279096

Locations
France
Besançon University Hospital
Besançon, France, 25000
Lille University Hospital
Lille, France, 59037
Sponsors and Collaborators
University Hospital, Lille
Centre Hospitalier Universitaire de Besancon
Saint-Louis Hospital, Paris, France
Assistance Publique - Hôpitaux de Paris
Hospices Civils de Lyon
University Hospital, Toulouse
Central Hospital, Nancy, France
University Hospital, Marseille
University Hospital, Bordeaux
Nantes University Hospital
Rennes University Hospital
Investigators
Principal Investigator: Brigitte Nelken, MD PhD Lille Unıversity Hospital, Lille, France
Study Chair: Pıerre S Rohrlich, MD, PhD Besancon University Hospital
  More Information

No publications provided

Responsible Party: Brigitte NELKEN, MD, University Hospital, Lille
ClinicalTrials.gov Identifier: NCT01279096     History of Changes
Other Study ID Numbers: 2009-010826-20, 2008_40/0905
Study First Received: January 17, 2011
Last Updated: July 30, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Lille:
Acute lymphoblastic leukemia
relapse
childhood
clofarabine

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Leukemia, Lymphoid
Recurrence
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes
Clofarabine
Asparaginase
Dexamethasone
Etoposide
Mitoxantrone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 22, 2014