Polatuzumab Vedotin, Rituximab, Ifosfamide, Carboplatin, and Etoposide (PolaR-ICE) as Initial Salvage Therapy for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Active:	No
Cancer Type:	Hematopoietic Malignancies Lymphoma Non-Hodgkin Lymphoma Unknown Primary	NCT ID:	NCT04665765
Trial Phases:	Phase II	Protocol IDs:	20148 (primary) NCI-2020-08524
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	City of Hope Comprehensive Cancer Center
NCI Full Details:	http://clinicaltrials.gov/show/NCT04665765

Summary

This phase II trial studies the effect of polatuzumab vedotin, rituximab, ifosfamide, carboplatin, and etoposide as initial salvage therapy in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Polatuzumab vedotin is a monoclonal antibody, polatuzumab, linked to a toxic agent called vedotin. Polatuzumab attaches to CD79b positive cancer cells in a targeted way and delivers vedotin to kill them. Rituximab is a monoclonal antibody. It binds to a protein 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. Chemotherapy drugs, such as ifosfamide, carboplatin, and etoposide, 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 chemotherapy with immunotherapy may kill more cancer cells in patients with diffuse large B-cell lymphoma.

Objectives

PRIMARY OBJECTIVES:
I. Evaluate the safety and tolerability of polatuzumab vedotin (Pola) added to rituximab, ifosfamide, carboplatin, and etoposide (PolaR-ICE) as first salvage therapy for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). (Safety Lead-in)
II. Evaluate the anti-tumor activity of PolaR-ICE as first salvage therapy for R/R DLBCL as assessed by the complete response rate after 2 cycles. (Phase 2)

SECONDARY OBJECTIVES:
I. Evaluate the overall response rate to PolaR-ICE as first salvage therapy for R/R DLBCL.
II. Evaluate the progression-free and overall survival of patients who received PolaR-ICE as first salvage therapy for R/R DLBCL followed by autologous stem cell transplantation (ASCT) and single-agent Pola consolidation after ASCT.
III. Evaluate the CR rate after Pola consolidation among those who were partial response (PR) at ASCT.
IV. Evaluate the toxicity of PolaR-ICE salvage therapy and that of Pola consolidation after ASCT.
V. Assess the rate of stem cell mobilization and collection failure in patients with R/R DLBCL who receive PolaR-ICE as first salvage therapy.

EXPLORATORY OBJECTIVES:
I. Assess the kinetics of circulating tumor deoxyribonucleic acid (DNA) after PolaR-ICE as first salvage therapy for R/R DLBCL followed by ASCT and single-agent Pola consolidation after ASCT.
II. Assess possible biomarkers of response to PolaR-ICE in patients with R/R DLBCL.
III. Examine the association between clinical outcomes (response, progression-free survival [PFS]) and pathological tumor characteristics.
IV. Examine the association between clinical outcomes (response, PFS) and circulating tumor (ct)DNA characteristics (mutation profile, kinetics of clearance).

OUTLINE:

SALVAGE THERAPY: Patients receive polatuzumab vedotin intravenously (IV) on day 1, rituximab IV on day 1, etoposide IV on days 1-3, carboplatin IV on day 2, and ifosfamide IV on day 2 or days 1-3. Treatment repeats every 21 days for up to 2-3 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response, partial response or stable disease by cycle 2 day 15 (C2D15) may receive 1 additional cycle of PolaR-ICE IV.

CONSOLIDATION THERAPY: Within 30-60 days after ASCT, patients receive polatuzumab vedotin IV on day 1. Treatment repeats every 21 days for up to 3-4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then periodically for up to 2 years.

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