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

NCT ID: NCT03864419

Last Updated: 2024-01-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-24

Study Completion Date

2023-07-26

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Rituximab and Hyaluronidase Human

Intervention Type BIOLOGICAL

Given SC

Cyclophosphamide

Intervention Type DRUG

Given IV

Vincristine

Intervention Type DRUG

Given IV

Methotrexate

Intervention Type DRUG

Given IV

Rituximab

Intervention Type BIOLOGICAL

Given IV

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.

Group Type EXPERIMENTAL

Rituximab and Hyaluronidase Human

Intervention Type BIOLOGICAL

Given SC

Cyclophosphamide

Intervention Type DRUG

Given IV

Vincristine

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Prednisone

Intervention Type DRUG

Given PO

Etoposide

Intervention Type DRUG

Given IV

Rituximab

Intervention Type BIOLOGICAL

Given IV

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.

Group Type EXPERIMENTAL

Rituximab and Hyaluronidase Human

Intervention Type BIOLOGICAL

Given SC

Cyclophosphamide

Intervention Type DRUG

Given IV

Vincristine

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Prednisone

Intervention Type DRUG

Given PO

Rituximab

Intervention Type BIOLOGICAL

Given IV

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.

Group Type EXPERIMENTAL

Rituximab and Hyaluronidase Human

Intervention Type BIOLOGICAL

Given SC

Rituximab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Rituximab and Hyaluronidase Human

Given SC

Intervention Type BIOLOGICAL

Cyclophosphamide

Given IV

Intervention Type DRUG

Vincristine

Given IV

Intervention Type DRUG

Methotrexate

Given IV

Intervention Type DRUG

Doxorubicin

Given IV

Intervention Type DRUG

Doxorubicin Hydrochloride

Given IV

Intervention Type DRUG

Prednisone

Given PO

Intervention Type DRUG

Etoposide

Given IV

Intervention Type DRUG

Rituximab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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Rituxan Hycela Rituximab Plus Hyaluronidase Rituximab/Hyaluronidase Rituximab/Hyaluronidase Human Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal LEUROCRISTINE VCR Vincrystine Abitrexate Alpha-Methopterin Amethopterin Brimexate Emthexat Emtexate Methotrexate LPF Methylaminopterin Methotrexatum Hydroxyl Daunorubicin Hydroxyldaunorubicin Adriamycine Adriblastina Doxolem Doxorubicin.HCl Deltacortene Decorton Decortisyl DeCortin Deltacortisone Econosone Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Vepesid 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

Eligibility Criteria

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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)
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Manoj Menon, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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UCI-Fred Hutch Cancer Centre

Kampala, , Uganda

Site Status

Countries

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Uganda

References

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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.

Reference Type DERIVED
PMID: 40184567 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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U028

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2019-01493

Identifier Type: REGISTRY

Identifier Source: secondary_id

10040

Identifier Type: OTHER

Identifier Source: secondary_id

RG1001799

Identifier Type: -

Identifier Source: org_study_id

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