Doxorubicin, Vinblastine, Dacarbazine, Brentuximab Vedotin, and Nivolumab in Treating Patients With Stage I-II Hodgkin Lymphoma

Classic Hodgkin Lymphoma Clinical Trial

Official title: A Phase II Trial of PET-Directed Therapy Using AVD (Doxorubicin, Vinblastine, and Dacarbazine) Plus Brentuximab Vedotin Induction Chemotherapy, With or Without Brentuximab Vedotin Plus Nivolumab, Followed by Nivolumab Consolidation for Patients With Previously Untreated Non-Bulky Limited Stage Hodgkin Lymphoma

Status Active, not recruiting

Clinical Trial Summary

This phase II trial evaluates how well AVD (doxorubicin, vinblastine, dacarbazine) in combination with brentuximab vedotin and nivolumab work in treating patients with stage I-II Hodgkin lymphoma. Drugs used in the chemotherapy, such as doxorubicin, vinblastine, dacarbazine, and brentuximab vedotin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, and/or by stopping them from spreading. Targeted agent, such as nivolumab, may interfere with the ability of cancer cells to grow and spread by enhancing the immune system. Giving doxorubicin, vinblastine, dacarbazine, brentuximab vedotin, and nivolumab may improve survival of patients with stage I-II Hodgkin lymphoma.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To estimate progression-free survival (PFS) at 3 years in patients with previously untreated stage I or II non-bulky Hodgkin lymphoma (HL) who received doxorubicin, vinblastine, dacarbazine (AVD) plus brentuximab vedotin (BV) induction therapy followed by nivolumab (N)VB consolidation therapy.

SECONDARY OBJECTIVES:

I. To estimate the overall survival (OS) rate at 3 years in patients with previously untreated stage I or II non-bulky HL who received AVD plus BV induction therapy followed by NVB consolidation therapy.

II. To estimate the percentage of patients with untreated stage I or II non-bulky HL who are positron emission tomography (PET) positive versus PET negative after 3 cycles of AVD plus BV induction therapy.

III. To estimate PFS and OS at 3 and 5 years separately for patients who are PET negative versus PET positive after 3 cycles of AVD plus BV induction followed by NVB consolidation therapy.

IV. To estimate time to progression (TTP) in patients with previously untreated stage I or II non-bulky HL who received AVD plus BV induction therapy followed by NVB consolidation therapy.

V. To estimate the overall response rate and the number of patients who convert to complete response (CMR) after NVB in patients with partial response (PMR) at the end of AVD plus BV induction therapy.

VI. To estimate the duration of response in patients with previously untreated stage I or II non-bulky Hodgkin's lymphoma who received AVD plus BV induction therapy followed by NVB consolidation therapy.

VII. To evaluate the toxicity and tolerability of AVD plus BV induction followed by NVB consolidation therapy as assessed via the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version [v]4).

EXPLORATORY OBJECTIVES:

I. Optional biopsy tissue samples will be collected for future analysis. II. Optional blood sample will be collected for future analysis. III. Cost-benefit analysis of AVD plus BV followed by NVB consolidation, compared to the current standard therapy with adriamycin, bleomycin, vinblastine plus dacarbazine (ABVD) with or without radiation therapy.

OUTLINE:

Patients receive doxorubicin intravenously (IV) over 3-5 minutes, vinblastine IV over 3-5 minutes, and dacarbazine IV over >= 30 minutes, and brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients with PET-positive then receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. PET-positive patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. PET-negative patients receive nivolumab IV over 30 minutes on day 1 starting after AVD and BV treatment. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 and 8 weeks, every 3 or 6 months for 2 years, and then once a year for 3 years. ;

Related Conditions & MeSH terms

• Ann Arbor Stage I Hodgkin Lymphoma
• Ann Arbor Stage IA Hodgkin Lymphoma
• Ann Arbor Stage IB Hodgkin Lymphoma
• Ann Arbor Stage II Hodgkin Lymphoma
• Ann Arbor Stage IIA Hodgkin Lymphoma
• Ann Arbor Stage IIB Hodgkin Lymphoma
• Classic Hodgkin Lymphoma
• Hodgkin Disease
• Lymphoma

• NCT number: NCT03233347
• Study type: Interventional
• Source: Academic and Community Cancer Research United
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 13, 2017
• Completion date: July 8, 2025