Trials / Active Not Recruiting
Active Not RecruitingNCT03749018
Nivolumab With DA-REPOCH Chemotherapy Regimen in Treating Patients With Aggressive B-Cell Non-Hodgkin's Lymphoma
A Phase II Study of Nivolumab in Combination With DA-REPOCH Followed by Short Course Nivolumab Consolidation in Patients With Aggressive B-Cell Non-Hodgkin's Lymphoma
- Status
- Active Not Recruiting
- Phase
- Phase 2
- Study type
- Interventional
- Enrollment
- 30 (estimated)
- Sponsor
- David Bond, MD · Academic / Other
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This phase II trial studies how well nivolumab works with the DA-REPOCH chemotherapy regimen in treating patients with aggressive B-cell non-Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body?s immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as dose-adjusted rituximab, etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (DA-REPOCH), work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab with DA-REPOCH may work better in treating patients with aggressive B-cell non-Hodgkin lymphoma.
Detailed description
PRIMARY OBJECTIVES: I. To determine 2-year progression-free survival (PFS) of nivolumab in combination with DA-REPOCH with short course nivolumab maintenance. SECONDARY OBJECTIVES: I. To determine the objective response rate (ORR), complete response (CR) rate, and duration of response to nivolumab in combination with DA REPOCH with short course nivolumab maintenance. II. To establish that nivolumab in combination with DA-REPOCH with short course nivolumab maintenance is feasible at standard dosing. III. To establish the toxicity profile of nivolumab in combination with DA-REPOCH with short course nivolumab maintenance at standard dosing. EXPLORATORY OBJECTIVES: I. To correlate the presence of major histocompatibility complex (MHC) class I and II by immunohistochemistry (IHC) with PFS. II. To correlate tumor and microenvironment expression of PD-L1 and microenvironment expression of PD-1 with PFS. III. To correlate cell of origin, MYC and Bcl-2 expression, Epstein-Barr virus (EBV)-positivity, and Ki67 proliferation index with response to treatment. IV. To determine the effect of nivolumab in combination with DA-REPOCH on immune cell subsets in the peripheral blood over time. V. To correlate circulating tumor (ct) deoxyribonucleic acid (DNA) with disease response by positron emission tomography (PET) imaging. VI. To track clonal evolution and detect the emergence of treatment-resistance by ct-DNA monitoring. OUTLINE: Patients receive rituximab intravenously (IV) and nivolumab IV over 60 minutes on day 1. Patients also receive etoposide, vincristine sulfate and doxorubicin hydrochloride IV continuously over 96 hours, cyclophosphamide IV bolus, and prednisone orally (PO) on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After course 6, patients receive nivolumab IV over 60 minutes on day 1 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 3 months for 3 years, and then every 6 months for 5 years.
Conditions
- Aggressive Non-Hodgkin Lymphoma
- Ann Arbor Stage I Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma
- Ann Arbor Stage II B-Cell Non-Hodgkin Lymphoma
- Ann Arbor Stage II Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma
- Ann Arbor Stage III B-Cell Non-Hodgkin Lymphoma
- Ann Arbor Stage III Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma
- Ann Arbor Stage IV B-Cell Non-Hodgkin Lymphoma
- Ann Arbor Stage IV Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma
- Diffuse Large B-Cell Lymphoma
- High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements
- High Grade B-Cell Lymphoma, Not Otherwise Specified
- Indolent Non-Hodgkin Lymphoma
- Mediastinal B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma
- Transformed Non-Hodgkin Lymphoma
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Cyclophosphamide | Given IV |
| DRUG | Doxorubicin Hydrochloride | Given IV |
| DRUG | Etoposide | Given IV |
| BIOLOGICAL | Nivolumab | Given IV |
| DRUG | Prednisone | Given PO |
| BIOLOGICAL | Rituximab | Given IV |
| DRUG | Vincristine Sulfate | Give IV |
Timeline
- Start date
- 2019-01-02
- Primary completion
- 2026-02-02
- Completion
- 2026-12-31
- First posted
- 2018-11-21
- Last updated
- 2026-02-06
Locations
1 site across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT03749018. Inclusion in this directory is not an endorsement.