Combination Chemotherapy With or Without Rituximab in Treating Younger Patients With Stage III-IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia - Full Text View

Purpose

This randomized phase II/III trial studies how well combination chemotherapy with or without rituximab works in treating younger patients with stage III-IV non-Hodgkin lymphoma or B-cell acute leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibody, such as rituximab, may block cancer growth in different ways by targeting certain cells. It is not yet known whether combination chemotherapy together with rituximab is more effective in treating patients with non-Hodgkin lymphoma or B-cell acute leukemia.

Condition	Intervention	Phase
Childhood B Acute Lymphoblastic Leukemia Childhood Burkitt Leukemia Childhood Diffuse Large Cell Lymphoma Mediastinal (Thymic) Large B-Cell Lymphoma Stage III Childhood Large Cell Lymphoma Stage IV Childhood Large Cell Lymphoma	Biological: Rituximab Drug: Prednisone Drug: Etoposide Drug: Doxorubicin Hydrochloride Drug: Cytarabine Drug: Vincristine Sulfate Drug: Cyclophosphamide Drug: Methotrexate Drug: Methylprednisolone Drug: Leucovorin Calcium Drug: Therapeutic Hydrocortisone Other: Laboratory Biomarker Analysis	Phase 2 Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	Intergroup Trial for Children or Adolescents With B-Cell NHL or B-AL: Evaluation of Rituximab Efficacy and Safety in High Risk Patients

Resource links provided by NLM:

Drug Information available for: Rituximab

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Burkitt Lymphoma Lymphosarcoma B-cell Lymphoma Diffuse Large B-Cell Lymphoma Lymphoma, Large-cell

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:

EFS [ Time Frame: 3 years ]
Will be estimated with the Kaplan Meier method. The 95% confidence intervals (95% CI) of the actuarial rates will be calculated with the Rothman method.

Secondary Outcome Measures:

Survival [ Time Frame: Up to 5 years ]
Estimated by the Kaplan-Meier method and the 95% confidence intervals (95% CI) of the actuarial rates calculated by the Rothman method.
Complete remission rate compared between arms by logistic regression [ Time Frame: Up to 5 years ]
Compared between arms by logistic regression.
Acute and long-term toxicity as assessed by the National Cancer Institute Common Terminology Criteria version 4.0 [ Time Frame: Up to 5 years ]
Immune reconstitution as assessed by Ig (G, A, and M) levels and lymphocyte counts [ Time Frame: Up to 5 years ]


Estimated Enrollment:	640
Study Start Date:	June 2012
Estimated Study Completion Date:	December 2020
Estimated Primary Completion Date:	December 2020 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Beginning 8 days later, patients receive rituximab IV on day 1; vincristine sulfate IV on day 1; prednisone PO BID or methylprednisolone IV on days 1-5; methotrexate IV over 3 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cyclophosphamide IV over 15 minutes on days 2-4; doxorubicin hydrochloride over 1 hour on day 2; and methotrexate IT and hydrocortisone IT on days 2 and 6. Treatment repeats every 18-21 days for 2 courses.	Biological: Rituximab Given IV Other Name: MOAB IDEC-C2B8 Drug: Prednisone Given PO or IV Drug: Etoposide Given IV Other Name: Lastet Drug: Doxorubicin Hydrochloride Given IV Drug: Vincristine Sulfate Given IV Other Names: Kyocristine Oncovin VCR Vincasar Drug: Cyclophosphamide Given IV Drug: Methotrexate Given IT Drug: Methylprednisolone Given IV Other Name: MePRDL Drug: Leucovorin Calcium Given PO Other Name: CF Drug: Therapeutic Hydrocortisone Given IT Other Names: Aeroseb-HC Cetacort HC Other: Laboratory Biomarker Analysis Correlative studies
Experimental: Arm II Beginning 8 days later, patients receive vincristine sulfate, prednisone or methylprednisolone, methotrexate, leucovorin calcium, cyclophosphamide, doxorubicin, methotrexate IT, and hydrocortisone IT as in arm I. Treatment repeats every 18-21 days for 2 courses.	Drug: Prednisone Given PO or IV Drug: Etoposide Given IV Other Name: Lastet Drug: Doxorubicin Hydrochloride Given IV Drug: Vincristine Sulfate Given IV Other Names: Kyocristine Oncovin VCR Vincasar Drug: Cyclophosphamide Given IV Drug: Methotrexate Given IT Drug: Methylprednisolone Given IV Other Name: MePRDL Drug: Leucovorin Calcium Given PO Other Name: CF Drug: Therapeutic Hydrocortisone Given IT Other Names: Aeroseb-HC Cetacort HC Other: Laboratory Biomarker Analysis Correlative studies
Experimental: Arm III Patients receive rituximab IV on days -2 (course 1) and 1; vincristine sulfate IV on day 1; prednisone PO or methylprednisolone IV on days 1-5; high-dose methotrexate IV over 4 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cyclophosphamide IV over 15 minutes on days 2-4; doxorubicin hydrochloride IV on day 2; and methotrexate IT, hydrocortisone IT, and cytarabine IT on days 2, 4, and 6. Treatment repeats every 21 days for 2 courses.	Biological: Rituximab Given IV Other Name: MOAB IDEC-C2B8 Drug: Prednisone Given PO or IV Drug: Doxorubicin Hydrochloride Given IV Drug: Cytarabine Given IV Other Names: CHX-3311 U-19920 Drug: Vincristine Sulfate Given IV Other Names: Kyocristine Oncovin VCR Vincasar Drug: Cyclophosphamide Given IV Drug: Methotrexate Given IT Drug: Methylprednisolone Given IV Other Name: MePRDL Drug: Therapeutic Hydrocortisone Given IT Other Names: Aeroseb-HC Cetacort HC Other: Laboratory Biomarker Analysis Correlative studies
Experimental: Arm IV Patients receive vincristine sulfate, prednisone or methylprednisolone, high-dose methotrexate, leucovorin calcium, cyclophosphamide, doxorubicin hydrochloride, and methotrexate, hydrocortisone, and cytarabine IT as in arm III.	Drug: Prednisone Given PO or IV Drug: Doxorubicin Hydrochloride Given IV Drug: Cytarabine Given IV Other Names: CHX-3311 U-19920 Drug: Vincristine Sulfate Given IV Other Names: Kyocristine Oncovin VCR Vincasar Drug: Cyclophosphamide Given IV Drug: Methotrexate Given IT Drug: Methylprednisolone Given IV Other Name: MePRDL Drug: Leucovorin Calcium Given PO Other Name: CF Drug: Therapeutic Hydrocortisone Given IT Other Names: Aeroseb-HC Cetacort HC Other: Laboratory Biomarker Analysis Correlative studies

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Eligibility


Ages Eligible for Study:	6 Months to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically or cytologically proven B-cell malignancies; either Burkitt leukemia or B-AL (= Burkitt leukemia = L3-AL), or diffuse large B-cell NHL, or aggressive mature B-cell NHL non otherwise specified or specifiable (phase III)
- Stage III with elevated LDH level (B-high) (LDH > twice the institutional upper limit of the adult normal values [> Nx2]), any stage IV, or B-AL (phase III)
Histolo-cytologically proven PMLBL (phase II)
- PMLBL without central nervous system (CNS) involvement
- Slides will be reviewed by the national pathology panel, but review is not mandatory before registration
Males and females of reproductive potential must agree to use an effective contraceptive method during the treatment, and after the end of treatment: during twelve months for women, taking into account the characteristics of rituximab and during five months for men, taking into account the characteristics of methotrexate
Complete initial work-up within 8 days prior to treatment that allows definite staging
Able to comply with scheduled follow-up and with management of toxicity
Signed informed consent from patients and/or their parents or legal guardians

Exclusion Criteria:

Follicular lymphoma, Mucosa-Associated Lymphoid Tissue (MALT) and nodular marginal zone are not included into this therapeutic study
In phase II study (PMLBL) patients with CNS involvement are not eligible
Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive human immunodeficiency virus (HIV) serology
Evidence of pregnancy or lactation period
There will be no exclusion criteria based on organ function
Past or current anti-cancer treatment except corticosteroids of less than 7 days duration in total
Tumor cell negative for cluster of differentiation (CD)20 (absence of result due to technical problems in the presence of other characteristics suggestive of BL/DLBCL, including genetic and phenotypic features, is not an exclusion criteria)
Prior exposure to rituximab
Severe active viral infection, especially hepatitis B; severe infection (such as sepsis, pneumonia, etc.) should be clinically controlled at the time of randomization; contact the national co-investigator for further advice if necessary
Hepatitis B carrier status history of hepatitis B virus (HBV) or positive serology; a patient is considered as HBV carrier or to have (had) HBV infection in case of:
- Unimmunized and hepatitis B surface antigen (HBsAg) and/or anti-HBs antibody and/or anti- HBc antibody positive,
- Immunized and HBsAG and/or anti-HBc antibody positive
  - Important note: for the phase III trial, a patient without a known history of hepatitis B could be randomized in the study if the serology results are not available at the time of the randomization; however, if the serology results are positive or not available at day 6 (the first day would be due to receive rituximab, if so randomized), the patient must be withdrawn from the study whatever the allocated treatment arm; the data center must be informed immediately; for the phase II trial, the hepatitis B serology results must be available before registration; in each case indicating a carrier status or history for hepatitis B infection, the patients must not receive rituximab, and therefore must not be included in the rituximab trials on any treatment arm; in case of high-risk patients, the recommendation is to treat these patients with the standard LMB regimen corresponding to the patient prognostic group; in the case of PMLBL the physician is left to choose the most appropriate therapy
Participation in another investigational drug clinical trial
Patients who, for any reason, are not able to comply with the national legislation

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: NCT01595048

Show 149 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Thomas Gross, PhD	Children's Oncology Group

More Information


Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT01595048 History of Changes
Other Study ID Numbers:	ANHL1131 NCI-2012-01963 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000732604 ( Other Identifier: Clinical trials.gov ) IGR2009/1593 2010-019224-31 ANHL1131 ( Other Identifier: Children's Oncology Group ) ANHL1131 ( Other Identifier: CTEP ) U10CA098543 ( U.S. NIH Grant/Contract ) U10CA180886 ( U.S. NIH Grant/Contract )
Study First Received:	May 8, 2012
Last Updated:	October 24, 2016

Additional relevant MeSH terms:


Lymphoma Leukemia Lymphoma, Non-Hodgkin Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Burkitt Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Epstein-Barr Virus Infections	Herpesviridae Infections DNA Virus Infections Virus Diseases Tumor Virus Infections Cyclophosphamide Methotrexate Cytarabine Rituximab Liposomal doxorubicin Doxorubicin Prednisone Etoposide Vincristine Methylprednisolone Hemisuccinate Prednisolone

ClinicalTrials.gov processed this record on September 21, 2017