RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating children who have relapsed or refractory acute lymphocytic leukemia.

Condition	Treatment or Intervention	Phase
L2 childhood acute lymphoblastic leukemia L1 childhood acute lymphoblastic leukemia recurrent childhood acute lymphoblastic leukemia	Procedure: chemotherapy  Drug: cytarabine  Drug: fludarabine  Drug: idarubicin	Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the complete response rate to combination fludarabine, idarubicin, and cytarabine in children with relapsed or refractory acute lymphocytic leukemia. II. Evaluate the safety and tolerance of this treatment in these patients. III. Evaluate the time to progression, disease free survival, and overall survival of these patients.

PROTOCOL OUTLINE: This is an open label, multicenter study. Patients receive idarubicin IV over 1 hour on days 1-3. Fludarabine IV is administered over 30 minutes on days 1-5. Cytarabine IV is administered over 4 hours on days 1-5. If partial response is obtained, patients receive a second course of treatment. Patients receive a consolidation course in the absence of disease progression and unacceptable toxicity. Idarubicin IV is administered over 1 hour on days 1 and 2. Fludarabine IV is administered over 30 minutes, followed by cytarabine IV over 4 hours on days 1-5. Patients are followed every 3 months for 2 years or until death.

PROJECTED ACCRUAL: A total of 24-45 patients will be accrued for this study within 27 months.

Ages Eligible for Study:  up to  17 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Cytologically diagnosed relapsed or refractory acute lymphocytic leukemia previously treated with front line therapy FAB L1 or L2
• Bone marrow relapse either isolated or associated with CNS or testicular relapse; Bone marrow blast cells greater than 10%; No isolated CNS relapse

--Prior/Concurrent Therapy--

• At least 6 months since prior autologous bone marrow transplantation
• No prior allogeneic bone marrow transplantation; No concurrent treatment with other experimental drug

--Patient Characteristics--

• Age: Under 18
• Performance status: WHO 0-2; Play-performance scale at least 60%
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin less than 2.5 times normal
• Renal: Creatinine less than 2.5 times normal
• Cardiovascular: No symptoms of cardiac failure; No decline of ejection fraction by more than 20% of the lower limit of normal; Shortening fraction at least 25%
• Other: No psychological, familial, sociological or geographical condition that would hamper compliance; No uncontrolled infection

Belgium
      Academisch Ziekenhuis der Vrije Universiteit Brussel, Brussels (Bruxelles),  1090,  Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
      Centre Hospitalier Regional de la Citadelle, Liege (Luik),  4000,  Belgium
      Clinique de l'Esperance, Montegnee,  4420,  Belgium
      Hopital Universitaire Des Enfants Reine Fabiola, Brussels (Bruxelles),  1020,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Gent, Ghent (Gent),  B-9000,  Belgium
France
      Centre Antoine Lacassagne, Nice,  06189,  France
      Centre Hospitalier Regional de Lille, Lille,  59037,  France
      Centre Hospitalier Regional et Universitaire d'Angers, Angers,  49033,  France
      CHR de Besancon - Hopital Saint-Jacques, Besancon,  25030,  France
      CHR de Grenoble - La Tronche, Grenoble,  38043,  France
      CHR Hotel Dieu, Nantes,  44093,  France
      CHU de Caen, Caen,  14033,  France
      Hopital Americain, Reims,  51092,  France
      Hopital Arnaud de Villeneuve, Montpellier,  34295,  France
      Hopital Debrousse, Lyon,  69322,  France
      Hopital des Enfants (Purpan Enfants), Toulouse,  31026,  France
      Hopital Jean Bernard, Poitiers,  86021,  France
      Hopital Robert Debre, Paris,  75019,  France
      Hopital Universitaire Hautepierre, Strasbourg,  67098,  France
      Institut Curie - Section Medicale, Paris,  75248,  France
Portugal
      Hospital Escolar San Joao, Porto,  4200,  Portugal

Study chairs or principal investigators

Antoine Thyss,  Study Chair,  EORTC Children's Leukemia Cooperative Group   

Study ID Numbers:  CDR0000066841; EORTC-58953
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003729
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08