TITLE:Less Intensive Therapy for Children With Non-Hodgkin's Lymphoma

NCT00002757 | Completed Phase 3 DMC

• 7 other identifiers: 5961COG-C5961CCG-5961SFOP-LMB-96CCLG-NHL-9600EU-96048CDR0000064702
• Study Type: interventional
• Target: 1,148
• Locations: 2 countries
• Sites: 2

Brief Summary

RATIONALE: Less intensive therapy may attain in the same results as intensive therapy in children with non-Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to study the effectiveness of less intensive therapy for children who have non-Hodgkin's lymphoma.

Conditions

Leukemia; Lymphoma

Keywords

childhood Burkitt lymphoma; untreated childhood acute lymphoblastic leukemia; L3 childhood acute lymphoblastic leukemia; stage I childhood small noncleaved cell lymphoma; stage I childhood large cell lymphoma; stage II childhood small noncleaved cell lymphoma; stage II childhood large cell lymphoma; stage III childhood small noncleaved cell lymphoma; stage III childhood large cell lymphoma; stage IV childhood small noncleaved cell lymphoma; stage IV childhood large cell lymphoma

Outcome Measures

Primary Outcomes (1)

• Event Free Survival

  Minimum time to death from any cause, relapse, or progressive disease, measured from the beginning of chemotherapy. Failure to respond to initial COP therapy, and biopsy positive residual disease at the third evaluation are not considered failures in this definition. However, death, relapse or disease progression following protocol mandated therapy intensification after these occurrences will be considered failures. In addition, biopsy positive residual disease at the completion of intensification is considered an event.

Secondary Outcomes (2)

• Conditional Survival

• Failure Free Survival

Study Arms (3)

Group A

ACTIVE COMPARATOR

All resected stage I and Abdominal stage II only. All Group A patients will be treated with two cycles of COPAD and will be followed in a confirmatory study of the current result of nearly 100% cure rate.

Biological: filgrastim; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate

Group B

ACTIVE COMPARATOR

Non resected stage I \& II, stage III \& st IV (CNS - ve, BM \< 25%). Patients with bulky disease are at risk from metabolic complications secondary to tumor lysis syndrome. Vigorous measures should be taken to minimise the risk of this. Prior to any chemotherapy being administered intravenous hydration fluids should be given run at a rate of 3000 mls/m2/day. Alkalinisation may be necessary Pay close attention to fluid balance and continue hydration fluids after the administration of COP for as long as the risk of tumour lysis persists.

Biological: filgrastim; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: methotrexate; Drug: prednisolone; Drug: prednisone; Drug: therapeutic hydrocortisone; Drug: vincristine sulfate

Group C

ACTIVE COMPARATOR

Bone marrow \> 25% but CNS negative Patients with bulky disease are at risk from metabolic complications secondary to tumor lysis syndrome. Vigorous measures should be taken to minimize the risk of this. Intravenous hydration fluids should be given prior to chemotherapy. Alkalinisation may be necessary. Monitor fluid balance and continue hydration fluids after the administration of COP for as long as the risk of tumor lysis persists

Biological: filgrastim; Drug: cyclophosphamide; Drug: cytarabine; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: methotrexate; Drug: prednisolone; Drug: therapeutic hydrocortisone; Drug: vincristine sulfate

Interventions

filgrastim BIOLOGICAL

Also known as: G-CSF, Neupogen, NSC-614629

Group A; Group B; Group C

cyclophosphamide DRUG

Also known as: NSC-26271

Group A; Group B; Group C

cytarabine DRUG

Also known as: NSC-63878

Group C

doxorubicin hydrochloride DRUG

Also known as: NSC-123127

Group A; Group B; Group C

etoposide DRUG

Also known as: VP16, NSC-141540

Group C

methotrexate DRUG

Also known as: NSC-740

Group B; Group C

prednisolone DRUG

Also known as: NSC-10023

Group B; Group C

prednisone DRUG

Also known as: NSC-10023

Group A; Group B

therapeutic hydrocortisone DRUG

Also known as: HYDROCORTISONE SODIUM SUCCINATE, NSC-10483

Group B; Group C

vincristine sulfate DRUG

Also known as: VCR, NSC-675574

Group A; Group B; Group C

Eligibility Criteria

• Age: Up to 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * One of the following diagnoses: * Newly diagnosed B-cell non-Hodgkin's lymphoma in Revised European-American Lymphoma (REAL) categories II 9, 10, and 11, i.e.: * Diffuse large cell * Burkitt's * High-grade B-cell, Burkitt's-like * L3 leukemia with greater than 5% blasts in bone marrow * No anaplastic large cell Ki1-positive lymphomas * Immunophenotype and Murphy stage required prior to randomization PATIENT CHARACTERISTICS: Age: * Over 6 months to under 21 years * Maximum age 18 years in France and the United Kingdom Other: * No congenital immunodeficiency * No prior organ transplantation * No prior malignancy * Not HIV positive * Available for at least 36 months of follow-up PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * No prior chemotherapy Endocrine therapy: * Steroids initiated no more than 72 hours prior to entry allowed * Bone marrow and cerebrospinal fluid examination required prior to steroids Radiotherapy: * Emergency radiotherapy initiated no more than 72 hours prior to entry allowed Surgery: * Not specified

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• Societe Francaise Oncologie Pediatrique: collaborator
• Children's Cancer and Leukaemia Group: collaborator

Study Sites (2)

Institut Gustave Roussy

Villejuif, F-94805, France

Location

Children's Hospital - Sheffield

Sheffield, England, S10 2TH, United Kingdom

Location

Related Publications (16)

• Lones MA, Raphael M, Perkins SL, Wotherspoon A, Auperin A, Terrier-Lacombe MJ, Sposto R, Weston C, Gerrard M, Patte C, Cairo MS, McCarthy K. Mature B-cell lymphoma in children and adolescents: International group pathologist consensus correlates with histology technical quality. J Pediatr Hematol Oncol. 2006 Sep;28(9):568-74. doi: 10.1097/01.mph.0000212980.67114.a5.

  PMID: 17006262 BACKGROUND

• Cairo MS, Sposto R, Gerrard M, Auperin A, Goldman SC, Harrison L, Pinkerton R, Raphael M, McCarthy K, Perkins SL, Patte C. Advanced stage, increased lactate dehydrogenase, and primary site, but not adolescent age (>/= 15 years), are associated with an increased risk of treatment failure in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB LMB 96 study. J Clin Oncol. 2012 Feb 1;30(4):387-93. doi: 10.1200/JCO.2010.33.3369. Epub 2012 Jan 3.

  PMID: 22215753 RESULT

• Shiramizu B, Goldman S, Kusao I, Agsalda M, Lynch J, Smith L, Harrison L, Morris E, Gross TG, Sanger W, Perkins S, Cairo MS. Minimal disease assessment in the treatment of children and adolescents with intermediate-risk (Stage III/IV) B-cell non-Hodgkin lymphoma: a children's oncology group report. Br J Haematol. 2011 Jun;153(6):758-63. doi: 10.1111/j.1365-2141.2011.08681.x. Epub 2011 Apr 18.

  PMID: 21496005 RESULT

• Nelson M, Perkins SL, Dave BJ, Coccia PF, Bridge JA, Lyden ER, Heerema NA, Lones MA, Harrison L, Cairo MS, Sanger WG. An increased frequency of 13q deletions detected by fluorescence in situ hybridization and its impact on survival in children and adolescents with Burkitt lymphoma: results from the Children's Oncology Group study CCG-5961. Br J Haematol. 2010 Feb;148(4):600-10. doi: 10.1111/j.1365-2141.2009.07967.x. Epub 2009 Nov 4.

  PMID: 19895612 RESULT

• Poirel HA, Cairo MS, Heerema NA, Swansbury J, Auperin A, Launay E, Sanger WG, Talley P, Perkins SL, Raphael M, McCarthy K, Sposto R, Gerrard M, Bernheim A, Patte C; FAB/LMB 96 International Study Committee. Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study. Leukemia. 2009 Feb;23(2):323-31. doi: 10.1038/leu.2008.312. Epub 2008 Nov 20.

  PMID: 19020548 RESULT

• Gerrard M, Cairo MS, Weston C, Auperin A, Pinkerton R, Lambilliote A, Sposto R, McCarthy K, Lacombe MJ, Perkins SL, Patte C; FAB LMB96 International Study Committee. Excellent survival following two courses of COPAD chemotherapy in children and adolescents with resected localized B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study. Br J Haematol. 2008 Jun;141(6):840-7. doi: 10.1111/j.1365-2141.2008.07144.x. Epub 2008 Mar 26.

  PMID: 18371107 RESULT

• Miles RR, Raphael M, McCarthy K, Wotherspoon A, Lones MA, Terrier-Lacombe MJ, Patte C, Gerrard M, Auperin A, Sposto R, Davenport V, Cairo MS, Perkins SL; SFOP/LMB96/CCG5961/UKCCSG/NHL 9600 Study Group. Pediatric diffuse large B-cell lymphoma demonstrates a high proliferation index, frequent c-Myc protein expression, and a high incidence of germinal center subtype: Report of the French-American-British (FAB) international study group. Pediatr Blood Cancer. 2008 Sep;51(3):369-74. doi: 10.1002/pbc.21619.

  PMID: 18493992 RESULT

• Cairo MS, Gerrard M, Sposto R, Auperin A, Pinkerton CR, Michon J, Weston C, Perkins SL, Raphael M, McCarthy K, Patte C; FAB LMB96 International Study Committee. Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents. Blood. 2007 Apr 1;109(7):2736-43. doi: 10.1182/blood-2006-07-036665.

  PMID: 17138821 RESULT

• Patte C, Auperin A, Gerrard M, Michon J, Pinkerton R, Sposto R, Weston C, Raphael M, Perkins SL, McCarthy K, Cairo MS; FAB/LMB96 International Study Committee. Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood. 2007 Apr 1;109(7):2773-80. doi: 10.1182/blood-2006-07-036673.

  PMID: 17132719 RESULT

• Goldman S, Gerrard M, Sposto R, et al.: Excellent results in children and adolescents with isolated mature B-acute lymphoblastic leukemia (B-ALL) (Burkitt): report from the French-American-British (FAB) international LMB study FAB/LMB96. [Abstract] Blood 106 (11): A-234, 2005.

  RESULT

• Poirel HA, Heerema NA, Swansbury J, et al.: In pediatric mature B-cell non Hodgkin's lymphoma (NHL), complex karyotype or del(13q) are linked prognostic factors in Burkitt lymphoma (BL) while 8q24/c-myc rearrangement is associated with a strong adverse effect in diffuse large B-cell lymphoma (DLBCL). [Abstract] Blood 106 (11): A-1905, 2005.

  RESULT

• Lones M, Perkins S, Sposto R, et al.: T-cell-rich large B-cell lymphoma (TCRLBCL) in children and adolescents treated on a B-large cell lymphoma trial: a report from the Children's Cancer Group (CCG) study CCG-5961. [Abstract] Ann Oncol 13(suppl 2): A-137, 45, 2002.

  RESULT

• Perkins S, Lones M, Sposto R, et al.: B-cell non-Hodgkin lymphoma (NHL) in children and adolescents: central phenotype results from Children's Cancer Group (CCG) study CCG-5961 and implications for future targeted bio-immune therapy (TBIT). [Abstract] Ann Oncol 13(suppl 2): A-136, 45, 2002.

  RESULT

• Sanger W, Lones M, Perkins S, et al.: Chromosome abnormalities in B-cell non-Hodgkin lymphoma (NHL) of children and adolescents: a report from Children's Cancer Group (CCG)study CCG-5961. [Abstract] Ann Oncol 13(suppl 2): A-138, 45, 2002.

  RESULT

• Perkins SL, Lones MA, Cairo MS, et al.: B-cell lymphoma/leukemia in children and adolescents: central phenotype results from Children's Cancer Group study (CCG)-5961 and implications for future Targeted Bio-Immune Therapy (TBIT). [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1520, 2001.

  RESULT

• Lones MA, Cairo MS, Perkins SL. T-cell-rich large B-cell lymphoma in children and adolescents: a clinicopathologic report of six cases from the Children's Cancer Group Study CCG-5961. Cancer. 2000 May 15;88(10):2378-86. doi: 10.1002/(sici)1097-0142(20000515)88:103.0.co;2-q.

  PMID: 10820362 RESULT

MeSH Terms

Conditions

Leukemia; Lymphoma; Burkitt Lymphoma; Dendritic Cell Sarcoma, Interdigitating

Interventions

Filgrastim; Granulocyte Colony-Stimulating Factor; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Methotrexate; Prednisolone; Prednisone; Hydrocortisone; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Histiocytic Disorders, Malignant; Histiocytosis

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Mitchell S. Cairo, MD

  Herbert Irving Comprehensive Cancer Center

  STUDY CHAIR

• Catherine Patte, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY CHAIR

• Mary P. Gerrard, MBChB, FRCP, FRCPCH

  Children's Hospital - Sheffield

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: June 1, 2001
• Primary Completion: October 1, 2003
• Study Completion: October 1, 2009
• Last Updated: July 24, 2014

Record last verified: 2014-07

Locations

GB (1); FR (1)