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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01595048
First received: May 8, 2012
Last updated: July 28, 2015
Last verified: July 2015
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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:


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

Primary Outcome Measures:
  • EFS [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
  • Immune reconstitution as assessed by Ig (G, A, and M) levels and lymphocyte counts [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 640
Study Start Date: June 2012
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   6 Months to 17 Years
Genders Eligible for Study:   Both
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 156 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Thomas Gross, PhD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01595048     History of Changes
Other Study ID Numbers: ANHL1131, NCI-2012-01963, CDR0000732604, IGR2009/1593, 2010-019224-31, ANHL1131, ANHL1131, U10CA098543, U10CA180886
Study First Received: May 8, 2012
Last Updated: July 28, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
DNA Virus Infections
Epstein-Barr Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Experimental
Tumor Virus Infections
Virus Diseases
Cortisol succinate
Cyclophosphamide
Cytarabine
Doxorubicin
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Leucovorin
Levoleucovorin

ClinicalTrials.gov processed this record on August 27, 2015