Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia
- Conditions
- LeukemiaLymphoma
- Registration Number
- NCT00002700
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells. Bone marrow transplantation can replace immune cells that were destroyed by chemotherapy.
PURPOSE: Randomized phase III trial to study the effectiveness of chemotherapy compared with or without bone marrow transplantation in treating patients with acute lymphoblastic leukemia.
- Detailed Description
OBJECTIVES:
* Compare the remission induction, toxicity, and duration of remission in patients with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma treated with prednisone vs dexamethasone plus cyclophosphamide, daunorubicin, and vincristine as induction.
* Compare the survival and disease-free survival of patients treated with autologous bone marrow transplantation (BMT) followed by low- or high-intensity maintenance chemotherapy with cranial irradiation after consolidation.
* Determine the relative and disease-free survival of patients treated with autologous or allogeneic BMT after identical induction, consolidation, and conditioning regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center and risk group (high vs standard).
Induction
* Patients are randomized to 1 of 2 treatment arms.
* Arm I:Patients receive daunorubicin IV on days 1-3 and 15 and 16; cyclophosphamide (CTX) IV on days 1 and 8; vincristine (VCR) IV on days 1, 8, 15, and 22; and prednisone IV or orally every 8 hours on days 1-7 and 15-21.
* Arm II: Patients receive daunorubicin, CTX, and VCR as in arm I and dexamethasone IV or orally on days 1-8 and 15-22.
* Patients on both arms without CNS disease at presentation receive CNS prophylaxis comprising methotrexate (MTX) intrathecally (IT) on days 1, 8, 15, and 22. Patients on both arms with CNS disease at presentation receive CNS therapy comprising hydrocortisone (HC) IT and MTX IT alternating with cytarabine (ARA-C) IT twice a week until CSF clears. After induction, patients on both arms proceed to consolidation, regardless of response.
Consolidation
* Patients receive ARA-C IV over 2 hours every 12 hours on days 29-34 and mitoxantrone IV on days 33-35. Patients without CNS disease at presentation receive CNS prophylaxis comprising MTX IT on day 29. Patients with CNS disease at presentation receive CNS therapy comprising HC IT and MTX IT alternating with ARA-C weekly for 6 weeks. Patients who achieve complete response (CR) at day 55-60 receive MTX IV on days 64 and 79, leucovorin calcium IV or orally every 6 hours on days 65-67 and 80-82, and asparaginase IV over 1 hour or intramuscularly on days 65 and 80.
* Standard-risk patients who are under age 20 and achieve CR after day 80 are assigned to arm IV of group A. Patients who achieve CR after day 80 and have a genotypically or phenotypically HLA-matched family donor, a family donor mismatched at only 1 locus (A, B, or DR), or an HLA-matched unrelated donor proceed to group B. Patients who achieve CR after day 80 and are eligible for autologous bone marrow transplantation (BMT) proceed to group A. Patients found to be at extremely high risk are taken off study.
Group A
* Patients are randomized to 1 of 2 treatment arms.
* Arm III: Autologous bone marrow is harvested. Patients receive bone marrow ablation comprising CTX IV over 1 hour on days -4 and -3 and total body irradiation on day -1. Autologous bone marrow is reinfused on day 0. Beginning at month 8 (4 months after BMT), patients receive first maintenance comprising VCR IV, doxorubicin IV, and dexamethasone IV (VAD) or VCR IV, doxorubicin IV, and prednisolone IV (VAP) on days 1-4 and 29-32. Patients receive second maintenance comprising oral mercaptopurine daily and oral MTX daily beginning at month 10 and continuing through year 3. Patients without CNS disease at presentation receive CNS prophylaxis comprising MTX IT on days 1 and 29. Patients with CNS disease at presentation receive CNS therapy comprising ARA-C IT, MTX IT, and HC IT beginning at 1 month after BMT and continuing monthly for 1 year and then every 3 months through year 3.
* Arm IV: Patients receive CTX IV and ARA-C IV continuously on day 1, oral mercaptopurine on days 8-28, and oral MTX on days 8, 15, and 22 during months 4, 7, 11, 13, 17, 21, 25, and 29. Patients receive MTX IV over 30 minutes on day 1, leucovorin calcium IV or orally every 6 hours on days 2-4, asparaginase IV over 1 hour or intramuscularly on day 2, oral mercaptopurine on days 8-28, and oral MTX on days 8, 15, and 22 during months 6, 10, 12, 15, 19, 23, and 27. Patients receive VAD or VAP as in arm III beginning at month 8. Patients without CNS disease at presentation receive CNS prophylaxis comprising whole brain radiotherapy and MTX IT on day 1 of radiotherapy during month 5. Patients with CNS disease at presentation receive CNS therapy as in arm III.
Group B
* Allogeneic bone marrow is harvested. Patients receive bone marrow ablation as in arm III beginning on day 100. Allogeneic bone marrow is infused over 15-30 minutes on day 0.
* Patients in groups A and B with CNS disease at presentation undergo radiotherapy to focal infiltration at entry or concurrently with total body irradiation, or whole brain radiotherapy during maintenance (if no prior CNS irradiation). At any time during the study, patients who develop marrow relapse (more than 5% leukemic blasts in bone marrow on 2 occasions), CNS relapse (blasts in CSF, cranial nerve palsy, or CNS mass), or testis or other extramedullary relapse are taken off study.
PROJECTED ACCRUAL: A total of 392 patients will be accrued for this study within approximately 6 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 392
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (44)
Institute of Hematology & Transfusiology, University Hospital
🇸🇰Bratislava, Slovakia
Hopital Universitaire Erasme
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
CHU Sart-Tilman
🇧🇪Liege, Belgium
Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni - Rotondo, Italy
Algemeen Ziekenhuis Middelheim
🇧🇪Antwerpen, Belgium
C.H.U. Saint-Pierre
🇧🇪Brussels, Belgium
A.Z. St. Jan
🇧🇪Brugge, Belgium
Ospedale Ferrarotto
🇮🇹Catania, Italy
University Hospital - Olomouc
🇨🇿Olomouc, Czech Republic
Centre Hospitalier Peltzer-La Tourelle
🇧🇪Verviers, Belgium
Ospedale S. Antonio Abate
🇮🇹Gallarate Varese, Italy
Ospedale S. Gennaro ASL NA1
🇮🇹Naples (Napoli), Italy
Policlinico - Cattedra di Ematologia
🇮🇹Palermo, Italy
Ospedale San Carlo
🇮🇹Potenza, Italy
Istituto di Ematologia Universita - University di Sassari
🇮🇹Sassari, Italy
Ospedale Molinette
🇮🇹Turin (Torino), Italy
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Universita Degli Studi di Bari Policlinico
🇮🇹Bari, Italy
A. Perrino Hospital
🇮🇹Brindisi, Italy
Policlinico di Careggi
🇮🇹Firenze (Florence), Italy
Ospedali Riuniti Foggia
🇮🇹Foggia, Italy
Ospedal SS Annunziata
🇮🇹Taranto, Italy
Hotel Dieu de Paris
🇫🇷Paris, France
University Medical Center Nijmegen
🇳🇱Nijmegen, Netherlands
Ospedale Civile Avellino
🇮🇹Avellino, Italy
Ospedale Santa Croce
🇮🇹Cuneo, Italy
Hopital Edouard Herriot
🇫🇷Lyon, France
Hospital Escolar San Joao
🇵🇹Porto, Portugal
Kreiskrankenhaus Meissen
🇩🇪Meissen, Germany
Ospedale Civile Alessandria
🇮🇹Alessandria, Italy
Ospedale Regionale A. Pugliese
🇮🇹Catanzaro, Italy
Ospedale Maggiore Lodi
🇮🇹Lodi, Italy
Policlinico Monteluce
🇮🇹Perugia, Italy
Ibn-i Sina Hospital
🇹🇷Ankara, Turkey
Ospedale Gen. Provinciale Santa Maria Goretti
🇮🇹Latina, Italy
University Hospital Rebro
ðŸ‡ðŸ‡·Zagreb, Croatia
Ospedale Di Montefiascone
🇮🇹Montefiascone, Italy
Groot Ziekengasthuis 's-Hertogenbosch
🇳🇱's-Hertogenbosch, Netherlands
Onze Lieve Vrouwe Gasthuis
🇳🇱Amsterdam, Netherlands
Maxima Medisch Centrum - locatie Eindhoven
🇳🇱Eindhoven, Netherlands
Hopital Necker
🇫🇷Paris, France
Centre Medico-Chirurgical Foch
🇫🇷Suresnes, France
Medical School/University of Zagreb
ðŸ‡ðŸ‡·Zagreb (Agram), Croatia