ANHL1131, Intergroup Trial for Children or Adolescents with B-cell Non-Hodgkin Lymphoma (NHL) or Mature B-cell Leukemia (B-AL): Evaluation of Rituximab Efficacy and Safety in High Risk Patients.
Ido Paz Priel
Johns Hopkins Kimmel Cancer Center in Baltimore
This is randomized phase II/III trail studies how well giving combination chemotherapy with or without rituximab works in treating younger patients with stages III or 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 to grow and spread. others find cancer cells and kill them or carry cancer-killing substances to them. It is not yet known whether giving combination chemotherapy together with rutuximab is more effective in treating patients with non-Hodgkin lymphoma or B-cell acute leukemia.
Histologically or cytologically proven B-cell malignancies; Burkitt leukemia or B-cell acute leukemia (B-AL) (Burkitt leukemia equal to 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 greater than twice the institutional upper of the adult normal values ( greater than 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 treatment, and after the end of treatment: 12 months for women 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-hepatitis B core (HBc) antibody positive Immunized 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 the time 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 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 rituxaimab
Experimental: Arm I Beginning 8 days later, patients recieve 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, 6, and etoposide. Treatment repeats ever 18-21 days for 2 courses. Experimental: Arm II Beginning 8 days later, patients recieve vincristine sulfate, prednisone or methylprednisolone, methotrexate, leucovorin calcium,cyclophosphamide, doxorubicin, methotrexate IT, therapeutic hydrocortisone ITas in arm I and etoposide. Treatment repeats ever 18-21 days for 2 courses. Experimental: Arm III Pantients receive rixtuximab 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 two courses. Experimental: Arm IV Patients receive vincristine sulfate, prednisone or methylpredisone, high dose methotrexate, leucovorin calcium, cyclophosphamide, doxorubicin hydrochloride, and methotrexate, therapeutic hydrocortisone, cytarabine IT as in arm III and etoposide.
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