Rituximab Hyaluronidase in Combination With Chemotherapy in Treating Aggressive B-cell Lymphoma in Uganda
Rituximab Hyaluronidase in Combination With Chemotherapy in Treating Aggressive B-cell Lymphoma in Uganda
This phase I trial studies how well rituximab hyaluronidase and combination chemotherapy work
 in treating patients in Uganda with Burkitt lymphoma, diffuse large B-cell lymphoma, or
 Kaposi sarcoma herpesvirus associated multicentric Castleman disease. Rituximab hyaluronidase
 is a combination of rituximab and hyaluronidase. Rituximab binds to a molecule called CD20,
 which is found on B cells (a type of white blood cell) and some types of cancer cells. This
 may help the immune system kill cancer cells. Hyaluronidase allows rituximab to be given by
 injection under the skin. Giving rituximab and hyaluronidase by injection under the skin is
 faster than giving rituximab alone by infusion into the blood. Drugs used in chemotherapy,
 such as cyclophosphamide, vincristine, methotrexate, etoposide, doxorubicin, and prednisone
 work in different ways to stop the growth of tumor cells, either by killing the cells, by
 stopping them from dividing, or by stopping them from spreading. While rituximab has a clear
 survival benefit in patients within developed countries, differences in supportive care and
 infectious co-morbidities require special attention. Giving rituximab hyaluronidase alone or
 in combination with chemotherapy may work better in treating patients with Burkitt lymphoma,
 diffuse large B-cell lymphoma, or Kaposi sarcoma herpesvirus associated multicentric
 Castleman disease compared to chemotherapy alone in Uganda.
OUTLINE:

 Open-label Phase I study characterizing the safety, tolerability, and activity of
 subcutaneous rituximab hyaluronidase (sqR) alone (KSHV-MCD), or combined with local standard
 of care chemotherapy (BL or DLBCL), in 2 age-based cohorts of patients:

 1. Cohort 1: Age >= 15

 2. Cohort 2: Age: 2-14

 sqR dose for Cohort 1 (adults) will be 1400 mg (flat dose); sqR dose for Cohort 2
 (pediatrics) will depend on patient weight: >= 35 kg: 1400 mg, < 35 kg: 700 mg. For all
 participants, sqR will be administered with local standard of care chemotherapy (BL, DLBCL)
 or alone (KSHV-MCD), and supportive care.

 Each cohort comprises two Therapy Groups. Therapy Group 1: up to 6 participants and will
 receive the first cycle of rituximab IV, and subsequent cycles as flat-dose sqR. Therapy
 Group 2: up to 12 participants and will receive flat-dose sqR for all cycles.

 Disease-specific chemotherapy to be administered with rituximab hyaluronidase include:

 PEDIATRIC BURKITT LYMPHOMA (BL): cyclophosphamide, vincristine and prednisone followed by 6
 cycles of cyclophosphamide, vincristine, and methotrexate (COP-COM).

 DLBCL: 6 cycles of cyclophosphamide, doxorubicin, vincristine and prednisone PO on days 1-5
 of cycle 1 (CHOP).

 ADULT BL: 6 cycles modified dose: etoposide, doxorubicin, vincristine, cyclophosphamide and
 prednisone PO on days 1-5 (adjusted EPOCH).

 KSHV-MCD: Rituximab or rituximab hyaluronidase SC on days 1, 8, 15, and 22.

 After completion of study treatment, patients are followed up at 30 days, 3, 6, 9 and 12
 months.
Inclusion Criteria:

 -  Histology and immunohistochemistry (CD20+) confirmed Burkitt lymphoma (BL), diffuse
 large B-cell lymphoma (DLBCL), or histology confirmed KSHV-associated multicentric
 Castleman disease with elevated blood KSHV viral load

 -  Cohort 1: Age should be equal to or greater than 15

 -  Cohort 2: Age: 2-15

 -  Measurable disease

 -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

 -  Able to provide informed consent (adults) or assent (children < 18 years) in English
 or Luganda

 -  Human immunodeficiency virus (HIV)-infected patients eligible if meet the following
 criteria:

 -  CD4+ T-cell count > 200 cells/uL

 -  HIV treatable with effective antiretroviral therapy that does not include agents
 with known significant drug-drug interactions with accompanying chemotherapy
 (ritonavir and cobicistat contraindicated)

 Exclusion Criteria:

 -  Previous therapy for lymphoma or KSHV-multicentric Castleman disease (MCD)

 -  History of hypersensitivity to rituximab

 -  Pregnant or nursing women. Men or women may not participate unless they have agreed to
 use effective contraception during treatment and for 12 months following completion of
 therapy

 -  Inadequate organ function, unless attributed to lymphoma or KSHV-MCD

 -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 times upper
 limit of normal

 -  Creatinine > 2 times upper limit than normal or calculated creatinine clearance < 60
 mL/min

 -  New York Heart Association (NYHA) cardiac failure class III or IV

 -  Patients with clinically significant anemia-hemoglobin less than 10 g/dL

 -  Central nervous system (CNS) masses consistent with lymphoma or untreated infection;
 leptomeningeal disease will not be excluded

 -  Patients with malignancy within 5 years, other than resected local skin cancer or
 limited Kaposi sarcoma (KS) (no known pulmonary KS)

 -  Patients with evidence of active infections including malaria and hepatitis B
 (participants with hepatitis B virus [HBV] controlled on antivirals will not be
 excluded)