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 February 2014 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: February 5, 2014
Last verified: February 2014
  Purpose

This randomized phase II/III trial studies how well giving combination chemotherapy with or without rituximab works in treating younger patients with stage III or stage 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 or by stopping them from dividing. Monoclonal antibody, such as rituximab, can block cancer cells growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving combination chemotherapy together with rituximab is more effective in treating patients with non-Hodgkin lymphoma or B-cell acute leukemia.


Condition Intervention Phase
B-cell Childhood Acute Lymphoblastic Leukemia
Childhood Diffuse Large Cell Lymphoma
L3 Childhood Acute Lymphoblastic Leukemia
Stage III Childhood Large Cell Lymphoma
Stage IV Childhood Large Cell Lymphoma
Untreated Childhood Acute Lymphoblastic Leukemia
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
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, therapeutic hydrocortisone IT on days 2 and 6 and etoposide. Treatment repeats every 18-21 days for 2 courses.
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: prednisone
Given PO or IV
Other Names:
  • DeCortin
  • Deltra
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: methotrexate
Given IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: methylprednisolone
Given IV
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Experimental: Arm II
Beginning 8 days later, patients receive vincristine sulfate, prednisone or methylprednisolone, methotrexate, leucovorin calcium, cyclophosphamide, doxorubicin, methotrexate IT, therapeutic hydrocortisone IT as in arm I and etoposide. Treatment repeats every 18-21 days for 2 courses.
Drug: prednisone
Given PO or IV
Other Names:
  • DeCortin
  • Deltra
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: methotrexate
Given IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: methylprednisolone
Given IV
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
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, therapeutic hydrocortisone IT, and cytarabine IT on days 2, 4, and 6. Treatment repeats every 21 days for 2 courses.
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: prednisone
Given PO or IV
Other Names:
  • DeCortin
  • Deltra
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: methotrexate
Given IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: methylprednisolone
Given IV
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Experimental: Arm IV
Patients receive vincristine sulfate, prednisone or methylprednisolone, high-dose methotrexate, leucovorin calcium, cyclophosphamide, doxorubicin hydrochloride, and methotrexate, therapeutic hydrocortisone, cytarabine IT as in arm III and etoposide.
Drug: prednisone
Given PO or IV
Other Names:
  • DeCortin
  • Deltra
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: methotrexate
Given IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: methylprednisolone
Given IV
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically proven B-cell malignancies; Burkitt leukemia or B-cell acute leukemia (B-AL) (Burkitt leukemia = L3-AL), or diffuse large B-cell non-Hodgkin lymphoma (NHL), or aggressive mature B-cell NHL not 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)
  • Histologically or cytologically proven primary mediastinal large B-cell lymphoma (PMLBL) (phase II)

    • No central nervous system (CNS) involvement
  • No follicular lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, or nodular marginal zone lymphoma
  • Tumor cell negative for CD20 (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)
  • Males and females of reproductive potential must agree to use an effective contraceptive method during the treatment, and after the end of treatment: 12 months for women and 5 months for men
  • Able to comply with scheduled follow-up and with management of toxicity
  • Signed informed consent from patients and/or their parents or legal guardians
  • No patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive human immunodeficiency virus (HIV) serology
  • Not pregnant or nursing
  • No severe active viral infection, especially hepatitis B virus (HBV)

    • Severe infection (such as sepsis, pneumonia, etc.) should be clinically controlled at the time of randomization
  • No HBV carrier status or positive serology; a patient is considered as HBV carrier or to have (had) HBV infection by any of the following criteria:

    • Unimmunized and hepatitis B surface antigen (HBsAg) and/or anti-HBs antibody and/or anti-hepatitis B core (HBc)-antibody positive
    • Immunized and HBsAg and/or anti-HBc antibody positive
    • For the Phase III trial, a patient without a known history of HBV 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 to receive rituximab, if so randomized), the patient must be withdrawn from the study whatever the allocated treatment arm; for the phase II trial, the hepatitis B serology results must be available before registration
  • No patients who, for any reason, are not able to comply with the national legislation
  • No past or current anti-cancer treatment except corticosteroids for less than one week
  • No participation in another investigational drug clinical trial
  • No prior exposure to rituximab
  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 106 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Thomas Gross 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, U10CA098543, COG-ANHL1131
Study First Received: May 8, 2012
Last Updated: February 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Antibodies, Monoclonal
Cyclophosphamide
Cytarabine
Methotrexate
Rituximab
Etoposide phosphate
Doxorubicin
Etoposide
Methylprednisolone Hemisuccinate
Prednisolone
Prednisone
Vincristine
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Methylprednisolone acetate
Prednisolone acetate

ClinicalTrials.gov processed this record on July 28, 2014