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Phase III Study of Intensive Chemotherapy for Children and Adolescents with NHL and B-Cell ALL
Basic Trial Information
Objectives I. Determine whether the response and relapse rates in patients with Stage III B-cell NHL presenting with high abdominal tumor burden (LDH greater than 500) can be improved by an intensified chemotherapy approach compared to historical controls. II. Determine whether CNS remission can be achieved by fractionated intraventricular chemotherapy in patients with B-cell NHL and B-cell ALL with initial CNS involvement. III. Determine whether survival of incomplete responders after 2 treatment cycles can be improved by escalating intensified chemotherapy, including ablative therapy with autologous bone marrow rescue, in patients with B-cell NHL and B-cell ALL. IV. Determine whether therapy intensity can be reduced from 3 to 2 cycles without an increased failure rate compared to historical controls in patients with B-cell NHL with complete initial resection. V. Determine whether patients with mediastinal T-cell lymphoma who have residual tumor after induction therapy can be cured without mediastinal irradiation. VI. Evaluate prospectively the dynamics of regression of lymphomatous tumors as prognostic indicators of outcome. VII. Evaluate prospectively the prognostic value of dose intensity during the first 3 cycles of therapy. Entry Criteria Disease Characteristics: Newly diagnosed non-Hodgkin's lymphoma of any type and B-cell acute lymphoblastic leukemia Previously misdiagnosed and inadequately treated NHL not eligible Prior/Concurrent Therapy: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy (other than a maximum of 2 doses of vincristine/daunorubicin within 4 weeks prior to entry) Endocrine therapy: No more than 4 weeks of prior corticosteroids Radiotherapy: No prior radiotherapy Surgery: Not specified Patient Characteristics: Age: Up to 18 Performance status: Any status Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: No significant morbidity from nonmalignant disease No history of a second malignancy Expected Enrollment Approximately 350 patients will be entered over a period of 2 years and 9 months. Outline The St. Jude staging system is used throughout. Non-B-cell NHL patients with Stage I/II disease are treated on Regimen SRG, while those with Stage III/IV disease are treated on Regimen RG. B-cell NHL and B-cell ALL patients who achieve initial complete resection are treated on Regimen R1; those with incomplete or no resection and those with no abdominal tumor or with abdominal tumor and LDH less than 500 are treated on Regimen R2, while those with abdominal tumor and LDH of 500 or above and/or bone marrow/CNS involvement and/or multiple bone lesions are treated on Regimen R3. Patients who fail therapy on Regimens R2 and R3 receive further therapy on Regimen BMT. Large cell anaplastic lymphoma patients with Stage I or completely resected Stage II disease are treated on Regimen K1, while those with incompletely resected Stage II or Stage III disease are treated on Regimen K2 and those with Stage IV disease are treated on Regimen K3. Patients failing therapy on Regimens K1, K2, and K3 receive further therapy on Regimen BMT. Regimen SRG: Induction: 7-Drug Combination Systemic Chemotherapy plus Single-Agent Intrathecal Chemotherapy. Prednisone, PRED, NSC-10023; Vincristine, VCR, NSC-67574; Daunorubicin, DNR, NSC-82151; Asparaginase, ASP; Cyclophosphamide, CTX, NSC-26271; Cytarabine, ARA-C, NSC-63878; Mercaptopurine, MP, NSC-755; plus Intrathecal Methotrexate, IT MTX, NSC-740. Intensification: 2-Drug Combination Systemic Chemotherapy/Leucovorin plus Single-Agent Intrathecal Chemotherapy. MP; MTX; Leucovorin calcium, CF, NSC-3590; plus IT MTX. Maintenance: 2-Drug Combination Systemic Chemotherapy. MP; MTX. Regimen RG: Induction: 7-Drug Combination Systemic Chemotherapy plus Single-Agent Intrathecal Chemotherapy. PRED; VCR; DNR; ASP; CTX; ARA-C; MP; plus IT MTX. Intensification: 2-Drug Combination Systemic Chemotherapy plus Single-Agent Intrathecal Chemotherapy. MP; MTX; plus IT MTX. Re-induction: 7-Drug Combination Systemic Chemotherapy plus Single-Agent Intrathecal Chemotherapy. Dexamethasone, DM, NSC-34521; VCR; Doxorubicin, DOX, NSC-123127; ASP; CTX; ARA-C; Thioguanine, TG, NSC-752; plus IT MTX. Cranial irradiation: Prophylactic/therapeutic cranial irradiation (equipment unspecified). Maintenance: 2-Drug Combination Systemic Chemotherapy. MP; MTX. Regimen R1: 2-Drug Combination Systemic Chemotherapy plus Triple Intrathecal Therapy (TIT) followed by 5-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT followed by 4-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT. Prephase V: DM; CTX; plus TIT (IT MTX, IT ARA-C, IT PRED); followed by Block A: DM; Ifosfamide, IFF, NSC-109724; MTX; Etoposide, VP-16, NSC-141540; ARA-C; CF; plus TIT; followed by Block B: CTX; DOX; DM; MTX; CF; plus TIT. Regimen R2: 2-Drug Combination Systemic Chemotherapy plus TIT followed by alternating courses of 6-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT and 5-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT. Prephase V; followed by alternating courses of Block AA: DM; IFF; VCR; MTX; VP-16; ARA-C; CF; plus TIT; and Block BB: CTX; DOX; DM; VCR; MTX; CF; plus TIT. 2 cycles (4 courses) of alternating therapy (AA-BB-AA-BB). Regimen R3: 2-Drug Combination Systemic Chemotherapy plus TIT followed by alternating courses of 6-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT and 5-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT. Prephase V; followed by alternating courses of Block AA and Block BB (with intraventricular or intrathecal TIT) for 3 cycles (6 courses) of alternating therapy (AA-BB-AA-BB-AA-BB). Regimen BMT: 3-Drug Combination Marrow-Ablative Systemic Chemotherapy followed by Bone Marrow Rescue. Busulfan, BU, NSC-750; VP-16; CTX (in patients without CNS disease) or Thiotepa, TSPA, NSC-6396 (in patients with CNS disease); followed by Autologous Bone Marrow Rescue, ABM. Regimen K1: 2-Drug Combination Systemic Chemotherapy plus TIT followed by 5-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT followed by 4-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT followed by 5-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT. Prephase V; followed by Block A; followed by Block B; followed by Block A. Regimen K2: 2-Drug Combination Systemic Chemotherapy plus TIT followed by alternating courses of 5-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT and 4-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT. Prephase V; followed by alternating courses of Block A and Block B for 3 cycles (6 courses) of alternating therapy (A-B-A-B-A-B). Regimen K3: 2-Drug Combination Systemic Chemotherapy plus TIT followed by alternating sequential courses of 6-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT, 5-Drug Combination Systemic Chemotherapy/Leucovorin plus TIT, and 4-Drug Combination Systemic Chemotherapy plus TIT. Prephase V; followed by alternating sequential courses of Block AA, Block BB, and Block CC: DM; Vindesine, DAVA, NSC-245467; ARA-C; VP-16; plus TIT. 2 cycles (6 courses) of alternating therapy (AA-BB-CC-AA-BB-CC).Published Results Seidemann K, Tiemann M, Schrappe M, et al.: Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. Blood 97 (12): 3699-706, 2001.[PUBMED Abstract] Reiter A, Schrappe M, Ludwig WD, et al.: Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM group report. Blood 95 (2): 416-21, 2000.[PUBMED Abstract] Reiter A, Schrappe M, Tiemann M, et al.: Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: A report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. Blood 94 (10): 3294-306, 1999.[PUBMED Abstract] Related PublicationsWössmann W, Schrappe M, Meyer U, et al.: Incidence of tumor lysis syndrome in children with advanced stage Burkitt's lymphoma/leukemia before and after introduction of prophylactic use of urate oxidase. Ann Hematol 82 (3): 160-5, 2003.[PUBMED Abstract] Attarbaschi A, Mann G, Dworzak M, et al.: Malignant non-Hodgkin's lymphoma of childhood and adolescence in Austria--therapy results between 1986 and 2000. Wien Klin Wochenschr 114 (23-24): 978-86, 2002.[PUBMED Abstract] Möricke A, Zimmermann M, Reiter A, et al.: Prognostic impact of age in children and adolescents with acute lymphoblastic leukemia: data from the trials ALL-BFM 86, 90, and 95. Klin Padiatr 217 (6): 310-20, 2005 Nov-Dec.[PUBMED Abstract] Reiter A, Schrappe M, Tiemann M, et al.: Successful treatment strategy for Ki-1 anaplastic large-cell lymphoma of childhood: a prospective analysis of 62 patients enrolled in three consecutive Berlin-Frankfurt-Munster group studies. J Clin Oncol 12 (5): 899-908, 1994.[PUBMED Abstract] Attarbaschi A, Mann G, Panzer-Grümayer R, et al.: Minimal residual disease values discriminate between low and high relapse risk in children with B-cell precursor acute lymphoblastic leukemia and an intrachromosomal amplification of chromosome 21: the Austrian and German acute lymphoblastic leukemia Berlin-Frankfurt-Munster (ALL-BFM) trials. J Clin Oncol 26 (18): 3046-50, 2008.[PUBMED Abstract] Müller J, Csóka M, Jakab Z, et al.: Treatment of pediatric non-Hodgkin lymphoma in Hungary: 15 years experience with NHL-BFM 90 and 95 protocols. Pediatr Blood Cancer 50 (3): 633-5, 2008.[PUBMED Abstract] Mann G, Attarbaschi A, Burkhardt B, et al.: Clinical characteristics and treatment outcome of infants with non-Hodgkin lymphoma. Br J Haematol 139 (3): 443-9, 2007.[PUBMED Abstract] Schrauder A, Reiter A, Gadner H, et al.: Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol 24 (36): 5742-9, 2006.[PUBMED Abstract] Trial Lead Organizations Medizinische Hochschule Hannover
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. |
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