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

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
Uganda
Study Type
Interventional
Intervention
Rituximab and Hyaluronidase Human
Cyclophosphamide
Vincristine
Methotrexate
Doxorubicin
Doxorubicin Hydrochloride
Prednisone
Etoposide
Rituximab
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Burkitt Lymphoma

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • UCI-Fred Hutch Cancer CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort I (pediatric BL)

Cohort II (DLBCL)

Cohort III (Adult BL)

Cohort IV (MCD)

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
Overall survival
Kaplan-Meier estimate
Progression-free survival
Kaplan-Meier estimate
Disease-free survival
Kaplan-Meier estimate

Full Information

First Posted
March 1, 2019
Last Updated
April 3, 2023
Sponsor
Fred Hutchinson Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03864419
Brief Title
Rituximab Hyaluronidase in Combination With Chemotherapy in Treating Aggressive B-cell Lymphoma in Uganda
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 24, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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: Cohort 1: Age >= 15 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Burkitt Lymphoma, KSHV-associated Multicentric Castleman Disease, Diffuse Large B-Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort I (pediatric BL)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort II (DLBCL)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort III (Adult BL)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort IV (MCD)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Rituximab and Hyaluronidase Human
Other Intervention Name(s)
Rituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase Human
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
LEUROCRISTINE, VCR, Vincrystine
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, Emthexat, Emtexate, Methotrexate LPF, Methylaminopterin, Methotrexatum
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Hydroxyl Daunorubicin, Hydroxyldaunorubicin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Doxorubicin Hydrochloride
Other Intervention Name(s)
Adriamycine, Adriblastina, Doxolem, Doxorubicin.HCl
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
Deltacortene, Decorton, Decortisyl, DeCortin, Deltacortisone, Econosone
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Vepesid
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
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
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events
Description
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.
Time Frame
Up to 12 months
Title
Number of participants that result in sufficient pharmacodynamic criteria
Description
Pharmacodynamic criteria is a Ctrough level above 25 ug/ml in children and adolescents after the first subcutaneous dose.
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Number of participants achieving a repose of complete response (CR)
Description
Response Evaluation Criteria in Solid Tumors (RECIST) criteria CR: complete disappearance of all target lesions.
Time Frame
1 year
Title
Overall survival
Description
Kaplan-Meier estimate
Time Frame
1 year
Title
Progression-free survival
Description
Kaplan-Meier estimate
Time Frame
1 year
Title
Disease-free survival
Description
Kaplan-Meier estimate
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
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 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Manoj Menon, MD
Phone
206.667.4636
Email
mmenon@fredhutch.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Manoj Menon, MD
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCI-Fred Hutch Cancer Centre
City
Kampala
Country
Uganda
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacqueline Asea
Phone
(256) 706915390
Email
jasea@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Jackson Orem, MBChB, MMed, PhD
First Name & Middle Initial & Last Name & Degree
Henry Ddungu, MD
First Name & Middle Initial & Last Name & Degree
Joyce Balagadde Kambugu, MBChB, MMed, CMO Paed (SA)

12. IPD Sharing Statement

Plan to Share IPD
No

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

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