Clinical Trials /

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

NCT03864419

Description:

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 monoclonal antibody, called rituximab, linked to a substance called hyaluronidase. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Hyaluronidase may help deliver rituximab into the body faster than giving rituximab alone. 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. Giving rituximab hyaluronidase and combination 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 combination chemotherapy alone.

Related Conditions:
  • Burkitt Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Multicentric Angiofollicular Lymphoid Hyperplasia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Rituximab Hyaluronidase and Combination Chemotherapy in Treating Patients in Uganda With Burkitt Lymphoma, Diffuse Large B-Cell Lymphoma, or Kaposi Sarcoma Herpesvirus Associated Multicentric Castleman Disease
  • 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 IDs

  • ORG STUDY ID: RG1001799
  • SECONDARY ID: U028
  • NCT ID: NCT03864419

Conditions

  • Burkitt Lymphoma
  • CD20 Positive
  • Diffuse Large B-Cell Lymphoma
  • HHV8-Positive Multicentric Castleman Disease

Interventions

DrugSynonymsArms
Rituximab and Hyaluronidase HumanRituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase HumanCohort I (pediatric BL)
CyclophosphamideCycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, CicloxalCohort I (pediatric BL)
VincristineLEUROCRISTINE, VCR, VincrystineCohort I (pediatric BL)
Vincristine SulfateKyocristine, Leurocristine sulfate, Oncovin, Vincasar, Vincosid, VincrexCohort I (pediatric BL)
MethotrexateAbitrexate, Alpha-Methopterin, Amethopterin, Brimexate, Emthexat, Emtexate, Methotrexate LPF, Methylaminopterin, MethotrexatumCohort I (pediatric BL)
DoxorubicinHydroxyl Daunorubicin, HydroxyldaunorubicinCohort II (DLBCL)
Doxorubicin HydrochlorideAdriamycine, Adriblastina, Doxolem, Doxorubicin.HClCohort II (DLBCL)
PrednisoneDeltacortene, Decorton, Decortisyl, DeCortin, Deltacortisone, EconosoneCohort II (DLBCL)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, VepesidCohort II (DLBCL)
Etoposide PhosphateEtopophosCohort II (DLBCL)

Purpose

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 monoclonal antibody, called rituximab, linked to a substance called hyaluronidase. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Hyaluronidase may help deliver rituximab into the body faster than giving rituximab alone. 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. Giving rituximab hyaluronidase and combination 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 combination chemotherapy alone.

Trial Arms

NameTypeDescriptionInterventions
Cohort I (pediatric BL)ExperimentalPatients 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 and hyaluronidase human IV or 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.
  • Rituximab and Hyaluronidase Human
  • Cyclophosphamide
  • Vincristine
  • Vincristine Sulfate
  • Methotrexate
Cohort II (DLBCL)ExperimentalPatients receive rituximab and hyaluronidase human IV or 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.
  • Rituximab and Hyaluronidase Human
  • Cyclophosphamide
  • Vincristine
  • Vincristine Sulfate
  • Doxorubicin
  • Doxorubicin Hydrochloride
  • Prednisone
  • Etoposide
  • Etoposide Phosphate
Cohort III (Adult BL)ExperimentalPatients receive rituximab and hyaluronidase human IV or 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.
  • Rituximab and Hyaluronidase Human
  • Cyclophosphamide
  • Vincristine
  • Doxorubicin
  • Doxorubicin Hydrochloride
  • Prednisone
Cohort IV (MCD)ExperimentalPatients receive rituximab and hyaluronidase human SC on days 1, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity.
  • Rituximab and Hyaluronidase Human

Eligibility 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

          -  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)

          -  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

          -  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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-emergent adverse events
Time Frame:Up to 12 months
Safety Issue:
Description:CTCAE v5.0 including unanticipated problems and grade 3-5 adverse events (AEs) at least probably related to subcutaneous rituximab hyaluronidase (sqR) administration.

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

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