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

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ClinicalTrials.gov Identifier: NCT03864419
Recruitment Status : Recruiting
First Posted : March 6, 2019
Last Update Posted : February 25, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

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.

Condition or disease Intervention/treatment Phase
Burkitt Lymphoma KSHV-associated Multicentric Castleman Disease Diffuse Large B-Cell Lymphoma Biological: Rituximab and Hyaluronidase Human Drug: Cyclophosphamide Drug: Vincristine Drug: Methotrexate Drug: Doxorubicin Drug: Doxorubicin Hydrochloride Drug: Prednisone Drug: Etoposide Biological: Rituximab Phase 1

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:

  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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 24, 2019
Estimated Primary Completion Date : May 4, 2023
Estimated Study Completion Date : May 4, 2023


Arm Intervention/treatment
Experimental: Cohort I (pediatric BL)
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
Given SC
Other Names:
  • Rituxan Hycela
  • Rituximab Plus Hyaluronidase
  • Rituximab/Hyaluronidase
  • Rituximab/Hyaluronidase Human

Drug: Cyclophosphamide
Given IV
Other Names:
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal

Drug: Vincristine
Given IV
Other Names:
  • LEUROCRISTINE
  • VCR
  • Vincrystine

Drug: Methotrexate
Given IV
Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • Emthexat
  • Emtexate
  • Methotrexate LPF
  • Methylaminopterin
  • Methotrexatum

Biological: Rituximab
Given IV
Other Names:
  • 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

Experimental: Cohort II (DLBCL)
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
Given SC
Other Names:
  • Rituxan Hycela
  • Rituximab Plus Hyaluronidase
  • Rituximab/Hyaluronidase
  • Rituximab/Hyaluronidase Human

Drug: Cyclophosphamide
Given IV
Other Names:
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal

Drug: Vincristine
Given IV
Other Names:
  • LEUROCRISTINE
  • VCR
  • Vincrystine

Drug: Doxorubicin
Given IV
Other Names:
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • Adriamycine
  • Adriblastina
  • Doxolem
  • Doxorubicin.HCl

Drug: Prednisone
Given PO
Other Names:
  • Deltacortene
  • Decorton
  • Decortisyl
  • DeCortin
  • Deltacortisone
  • Econosone

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Vepesid

Biological: Rituximab
Given IV
Other Names:
  • 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

Experimental: Cohort III (Adult BL)
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
Given SC
Other Names:
  • Rituxan Hycela
  • Rituximab Plus Hyaluronidase
  • Rituximab/Hyaluronidase
  • Rituximab/Hyaluronidase Human

Drug: Cyclophosphamide
Given IV
Other Names:
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal

Drug: Vincristine
Given IV
Other Names:
  • LEUROCRISTINE
  • VCR
  • Vincrystine

Drug: Doxorubicin
Given IV
Other Names:
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • Adriamycine
  • Adriblastina
  • Doxolem
  • Doxorubicin.HCl

Drug: Prednisone
Given PO
Other Names:
  • Deltacortene
  • Decorton
  • Decortisyl
  • DeCortin
  • Deltacortisone
  • Econosone

Biological: Rituximab
Given IV
Other Names:
  • 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

Experimental: Cohort IV (MCD)
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
Given SC
Other Names:
  • Rituxan Hycela
  • Rituximab Plus Hyaluronidase
  • Rituximab/Hyaluronidase
  • Rituximab/Hyaluronidase Human

Biological: Rituximab
Given IV
Other Names:
  • 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




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events [ Time Frame: Up to 12 months ]
    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.

  2. Number of participants that result in sufficient pharmacodynamic criteria [ Time Frame: Up to 12 months ]
    Pharmacodynamic criteria is a Ctrough level above 25 ug/ml in children and adolescents after the first subcutaneous dose.


Secondary Outcome Measures :
  1. Number of participants achieving a repose of complete response (CR) [ Time Frame: 1 year ]
    Response Evaluation Criteria in Solid Tumors (RECIST) criteria CR: complete disappearance of all target lesions.

  2. Overall survival [ Time Frame: 1 year ]
    Kaplan-Meier estimate

  3. Progression-free survival [ Time Frame: 1 year ]
    Kaplan-Meier estimate

  4. Disease-free survival [ Time Frame: 1 year ]
    Kaplan-Meier estimate



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03864419


Contacts
Layout table for location contacts
Contact: Thomas Uldrick, MD, MS 206-667-7485 tuldrick@fredhutch.org

Locations
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Uganda
UCI-Fred Hutch Cancer Centre Recruiting
Kampala, Uganda
Contact: Jacqueline Asea    (256) 706915390    jasea@fredhutch.org   
Principal Investigator: Jackson Orem, MBChB, MMed, PhD         
Principal Investigator: Henry Ddungu, MD         
Principal Investigator: Joyce Balagadde Kambugu, MBChB, MMed, CMO Paed (SA)         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Thomas Uldrick, MD, MS Fred Hutchinson Cancer Research Center
Layout table for additonal information
Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT03864419    
Other Study ID Numbers: RG1001799
U028 ( Other Identifier: FHCRC )
NCI-2019-01493 ( Registry Identifier: NCI / CTRP )
P30CA015704 ( U.S. NIH Grant/Contract )
10040 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
First Posted: March 6, 2019    Key Record Dates
Last Update Posted: February 25, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Burkitt Lymphoma
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Castleman Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Liposomal doxorubicin
Methotrexate
Etoposide
Vincristine
Daunorubicin
Podophyllotoxin
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins