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 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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
RG1001799
- SECONDARY ID:
U028
- SECONDARY ID:
NCI-2019-01493
- SECONDARY ID:
P30CA015704
- SECONDARY ID:
10040
- NCT ID:
NCT03864419
Conditions
- Burkitt Lymphoma
- KSHV-associated Multicentric Castleman Disease
- Diffuse Large B-Cell Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
Rituximab and Hyaluronidase Human | Rituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase Human | Cohort I (pediatric BL) |
Cyclophosphamide | Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal | Cohort I (pediatric BL) |
Vincristine | LEUROCRISTINE, VCR, Vincrystine | Cohort I (pediatric BL) |
Methotrexate | Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, Emthexat, Emtexate, Methotrexate LPF, Methylaminopterin, Methotrexatum | Cohort I (pediatric BL) |
Doxorubicin | Hydroxyl Daunorubicin, Hydroxyldaunorubicin | Cohort II (DLBCL) |
Doxorubicin Hydrochloride | Adriamycine, Adriblastina, Doxolem, Doxorubicin.HCl | Cohort II (DLBCL) |
Prednisone | Deltacortene, Decorton, Decortisyl, DeCortin, Deltacortisone, Econosone | Cohort II (DLBCL) |
Etoposide | Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Vepesid | Cohort II (DLBCL) |
Rituximab | 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 | Cohort I (pediatric BL) |
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 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:
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Cohort I (pediatric BL) | Experimental | 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. | - Rituximab and Hyaluronidase Human
- Cyclophosphamide
- Vincristine
- Methotrexate
- Rituximab
|
Cohort II (DLBCL) | Experimental | 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. | - Rituximab and Hyaluronidase Human
- Cyclophosphamide
- Vincristine
- Doxorubicin
- Doxorubicin Hydrochloride
- Prednisone
- Etoposide
- Rituximab
|
Cohort III (Adult BL) | Experimental | 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. | - Rituximab and Hyaluronidase Human
- Cyclophosphamide
- Vincristine
- Doxorubicin
- Doxorubicin Hydrochloride
- Prednisone
- Rituximab
|
Cohort IV (MCD) | Experimental | 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. | - Rituximab and Hyaluronidase Human
- Rituximab
|
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)
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: | 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. |
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: | Recruiting |
Lead Sponsor: | Fred Hutchinson Cancer Research Center |
Last Updated
August 30, 2021