Nivolumab, Ifosfamide, Carboplatin, and Etoposide as Second-Line Therapy in Treating Patients With Refractory or Relapsed HL

Refractory Hodgkin Lymphoma Clinical Trial

Official title: A Phase II Trial of Response-Adapted Second-Line Therapy for Hodgkin Lymphoma Using Anti-PD-1 Antibody Nivolumab ? ICE Chemotherapy as a Bridge to Autologous Hematopoietic Cell Transplant (NICE Trial)

Status Active, not recruiting

Clinical Trial Summary

This phase II trial studies the side effects of nivolumab and to see how well it works when given together with ifosfamide, carboplatin, and etoposide in treating patients with Hodgkin lymphoma that has come back (relapsed) and does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies such as nivolumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, 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 nivolumab, ifosfamide, carboplatin and etoposide may work better in treating patients with Hodgkin lymphoma.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Evaluate the anti-tumor activity of nivolumab as single agent and in combination with ifosfamide, carboplatin, etoposide (ICE) chemotherapy (nivolumab [N]ICE) as assessed by complete response (CR) rate prior to autologous hematopoietic cell transplantation.

II. To estimate the proportion of patients experiencing unacceptable adverse events. (Cohort B) III. To assess the safety and tolerability of nivolumab + ICE chemotherapy through evaluation of toxicities, including type, frequency, severity, attribution, time course, and duration. (Cohort B) IV. To obtain estimate of overall response rate (ORR), complete response rate, response duration and survival (overall and event-free). (Cohort B) V. Summarize stem cell mobilization outcomes (e.g., total CD34+ cell yield, number of apheresis days, proportion of patients who achieve >= 2 x 10^6 CD34+ cells/kg). (Cohort B) VI. Evaluate Hodgkin lymphoma biological markers in subjects treated with nivolumab. (Cohort B)

SECONDARY OBJECTIVES:

I. Assess the safety and tolerability of nivolumab +/- ICE chemotherapy through evaluation of toxicities, including type, frequency, severity, attribution, time course and duration.

II. Obtain estimates of overall response rate (ORR), response duration and survival (overall and event-free).

III. Summarize stem cell mobilization outcomes (e.g., total CD34+ cell yield, number of apheresis days, proportion of patients who achieve >= 2 x 10^6 CD34+ cells/kg).

IV. Evaluate Hodgkin lymphoma biological markers in subjects treated with nivolumab.

V. Among subjects who undergo autologous hematopoietic cell transplantation (AHCT), estimate the post-AHCT overall/progression free survival (PFS) probability and cumulative incidence of relapse/progression, non-relapse mortality (NRM) at 100-days, 1-year and 2-years.

VI. Among subjects who undergo autologous hematopoietic cell transplantation (AHCT), characterize post-AHCT toxicities during the first 30- and 100- days post stem cell infusion by type, frequency, severity, attribution, time course and duration.

VII. Among subjects who undergo autologous hematopoietic cell transplantation (AHCT), evaluate short and long-term post-AHCT complications, including: delayed engraftment (neutrophil and platelet) and infection, graft versus host disease and sinusoidal obstruction syndrome.

EXPLORATORY OBJECTIVES:

I. Collect deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) from lymphoma specimens and serial plasma samples for future biomarker evaluation.

II. Evaluate potential changes in Hodgkin lymphoma biological markers of patients treated with nivolumab.

OUTLINE: Patients are sequentially assigned to 1 of 2 cohorts.

COHORT A: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 14 days for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients with CR or partial response (PR) receive nivolumab for an additional 6 weeks. Patients with only stable disease (SD) after 6-week nivolumab treatment receive nivolumab for an additional 6 weeks or receive nivolumab IV over 30 minutes on day 1, etoposide IV on days 1-3, ifosfamide IV continuously over 24 hours on day 2, and carboplatin IV on day 2 every 21 days for 6 weeks per physician/investigator's discretion. Patients with progressive disease (PD) after 6-week nivolumab treatment or patients with PR, SD, or PD after 12-week nivolumab treatment receive nivolumab IV over 30 minutes on day 1, etoposide IV on days 1-3, ifosfamide IV continuously over 24 hours on day 2, and carboplatin IV on day 2. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

COHORT B: Patients receive nivolumab IV over 30 minutes on cycle 1 (cycle 1 is 14 days), day 1 in the absence of disease progression or unacceptable toxicity. Beginning in cycle 2, patients receive nivolumab IV over 30 minutes on day 1, etoposide IV on days 1-3, ifosfamide IV continuously over 24 hours on day 2, and carboplatin IV on day 2. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 2 years. ;

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma
• Recurrent Hodgkin Lymphoma
• Refractory Hodgkin Lymphoma

• NCT number: NCT03016871
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 24, 2017
• Completion date: January 30, 2026