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

Diffuse Large B-Cell Lymphoma Clinical Trial

Official title:

A Phase I Study of Subcutaneous Rituximab Hyaluronidase Combined With Local Standard-of-Care Chemotherapy for the Treatment of Burkitt Lymphoma, Diffuse Large B-Cell Lymphoma or as Monotherapy for Kaposi Sarcoma Herpesvirus Associated Multicentric Castleman Disease in Pediatrics and Adults in Uganda

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03864419
• Other study ID #: RG1001799
• Secondary ID: U028NCI-2019-014
• Status: Terminated
• Phase: Phase 1
• Start date: October 24, 2019
• Est. completion date: July 26, 2023

Study information

• Verified date: December 2023
• Source: Fred Hutchinson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: July 26, 2023
• Est. primary completion date: July 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Biological:
• Rituximab and Hyaluronidase Human
Given SC

Drug:
• Cyclophosphamide
Given IV
• Vincristine
Given IV
• Methotrexate
Given IV
• Doxorubicin
Given IV
• Doxorubicin Hydrochloride
Given IV
• Prednisone
Given PO
• Etoposide
Given IV

Biological:
• Rituximab
Given IV

Locations

Country	Name	City	State
Uganda	UCI-Fred Hutch Cancer Centre	Kampala

Sponsors (1)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Center

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Number of participants achieving a repose of complete response (CR)	Response Evaluation Criteria in Solid Tumors (RECIST) criteria CR: complete disappearance of all target lesions.	1 year
Secondary	Overall survival	Kaplan-Meier estimate	1 year
Secondary	Progression-free survival	Kaplan-Meier estimate	1 year
Secondary	Disease-free survival	Kaplan-Meier estimate	1 year