Rituximab Hyaluronidase in Combination With Chemotherapy in Treating Aggressive B-cell Lymphoma in Uganda

• Status: Recruiting
• Trial end date: 2023-05-04
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fred Hutchinson Cancer Research Center
• Treatments: Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cyclophosphamide; Daunorubicin; Doxorubicin; Etoposide; Immunoglobulins; Liposomal doxorubicin; Methotrexate; Podophyllotoxin; Prednisone; Rituximab; Vincristine

Criteria

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)