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

NCT03864419 | Terminated Phase 1 DMC FDA Drug

• 4 other identifiers: RG1001799U028NCI-2019-0149310040
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Burkitt Lymphoma; KSHV-associated Multicentric Castleman Disease; Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-emergent adverse events

  Common Terminology Criteria for Adverse Events version 5.0 including unanticipated problems and grade 3-5 adverse events (AEs) at least probably related to subcutaneous rituximab hyaluronidase (sqR) administration.

  Up to 12 months

• Number of participants that result in sufficient pharmacodynamic criteria

  Pharmacodynamic criteria is a Ctrough level above 25 ug/ml in children and adolescents after the first subcutaneous dose.

  Up to 12 months

Secondary Outcomes (4)

• Number of participants achieving a repose of complete response (CR)

  1 year

• Overall survival

  1 year

• Progression-free survival

  1 year

• Disease-free survival

  1 year

Study Arms (4)

Cohort I (pediatric BL)

EXPERIMENTAL

Patients receive cyclophosphamide IV and vincristine IV on day 1, and prednisone IV or PO on days 1-7 in the absence of disease progression or unacceptable toxicity. Patients then receive rituximab IV or rituximab hyaluronidase SC, cyclophosphamide IV, vincristine IV, and methotrexate IV on day 1. Cycles repeat every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Rituximab and Hyaluronidase Human; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Methotrexate; Biological: Rituximab

Cohort II (DLBCL)

EXPERIMENTAL

Patients receive rituximab IV or rituximab and hyaluronidase human SC, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1, and prednisone PO on days 1-5 of cycle 1. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Rituximab and Hyaluronidase Human; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Prednisone; Drug: Etoposide; Biological: Rituximab

Cohort III (Adult BL)

EXPERIMENTAL

Patients receive rituximab IV or rituximab and hyaluronidase human SC in day 1, etoposide IV, doxorubicin IV, and vincristine IV on days 1-4. Patients also receive cyclophosphamide IV on day 5 and prednisone PO on days 1-5. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Rituximab and Hyaluronidase Human; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Prednisone; Biological: Rituximab

Cohort IV (MCD)

EXPERIMENTAL

Patients receive rituximab IV or rituximab and hyaluronidase human SC on days 1, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity.

Biological: Rituximab and Hyaluronidase Human; Biological: Rituximab

Interventions

Rituximab and Hyaluronidase Human BIOLOGICAL

Given SC

Also known as: Rituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase Human

Cohort I (pediatric BL); Cohort II (DLBCL); Cohort III (Adult BL); Cohort IV (MCD)

Cyclophosphamide DRUG

Given IV

Also known as: Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal

Cohort I (pediatric BL); Cohort II (DLBCL); Cohort III (Adult BL)

Vincristine DRUG

Given IV

Also known as: LEUROCRISTINE, VCR, Vincrystine

Cohort I (pediatric BL); Cohort II (DLBCL); Cohort III (Adult BL)

Methotrexate DRUG

Given IV

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, Emthexat, Emtexate, Methotrexate LPF, Methylaminopterin, Methotrexatum

Cohort I (pediatric BL)

Doxorubicin DRUG

Given IV

Also known as: Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Cohort II (DLBCL); Cohort III (Adult BL)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: Adriamycine, Adriblastina, Doxolem, Doxorubicin.HCl

Cohort II (DLBCL); Cohort III (Adult BL)

Prednisone DRUG

Given PO

Also known as: Deltacortene, Decorton, Decortisyl, DeCortin, Deltacortisone, Econosone

Cohort II (DLBCL); Cohort III (Adult BL)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Vepesid

Cohort II (DLBCL)

Rituximab BIOLOGICAL

Given IV

Also known as: BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar JHL1101, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, RTXM83, Truxima

Cohort I (pediatric BL); Cohort II (DLBCL); Cohort III (Adult BL); Cohort IV (MCD)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

UCI-Fred Hutch Cancer Centre

Kampala, Uganda

Location

Related Publications (1)

• Menon MP, Ddungu H, Mubiru KR, Adams SV, Asea J, Namagembe R, Namuli P, Kambugu J, Towlerton AMH, Puronen C, Uldrick TS, Orem J, Warren EH. Phase I Study of Subcutaneous Rituximab Hyaluronidase Combined With CHOP Chemotherapy for the Treatment of Diffuse Large B-Cell Lymphoma in Uganda. JCO Glob Oncol. 2025 Apr;11:e2400489. doi: 10.1200/GO-24-00489. Epub 2025 Apr 4.

  PMID: 40184567 DERIVED

MeSH Terms

Conditions

Burkitt Lymphoma; Multi-centric Castleman's Disease; Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Hyaluronoglucosaminidase; Cyclophosphamide; Vincristine; Methotrexate; Doxorubicin; Prednisone; deltacortene; Etoposide; CT-P10

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Aminopterin; Pterins; Pteridines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Study Officials

• Manoj Menon, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 6, 2019
• Study Start: October 24, 2019
• Primary Completion: July 26, 2023
• Study Completion: July 26, 2023
• Last Updated: January 3, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)