A Phase 2 Study of Brentuximab Vedotin Plus Nivolumab in Patients With Relapsed/Refractory Hodgkin Lymphoma Previously Treated With Brentuximab or Checkpoint Inhibitors
Overview
- Phase
- Phase 2
- Intervention
- Brentuximab Vedotin
- Conditions
- Recurrent Classic Hodgkin Lymphoma
- Sponsor
- Emory University
- Enrollment
- 46
- Locations
- 2
- Primary Endpoint
- Overall response rate (ORR)
- Status
- Recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
This phase II trial studies the effect of brentuximab vedotin and nivolumab in treating patients with classic Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory) that have been previously treated with brentuximab vedotin or checkpoint inhibitors. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. 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. Giving brentuximab vedotin and nivolumab in combination may be an effective treatment in patients with relapsed or refractory classic Hodgkin lymphoma previously treated with brentuximab vedotin or checkpoint inhibitors.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the overall response rate (ORR) with brentuximab vedotin (brentuximab)/nivolumab used in combination in patients in patients previously treated with brentuximab in combination with standard chemotherapy for Hodgkin lymphoma (HL). II. To determine the ORR with brentuximab/nivolumab in combination in patients previously treated with checkpoint inhibitors alone or in combination with standard chemotherapy for HL. SECONDARY OBJECTIVES: I. To determine the complete response rate (CRR) and progression-free survival (PFS) with brentuximab/nivolumab in patients previously treated with brentuximab in combination with standard chemotherapy for HL. II. To determine the CRR and PFS with brentuximab/nivolumab in patients previously treated with checkpoint inhibitors alone or in combination with standard chemotherapy for HL. III. To evaluate safety of this regimen using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 (v 5.0). IV. To determine the tolerability of this regimen using patient-reported outcomes including Patient Reported Outcomes (PRO)-CTCAE or pediatric PRO-CTCAE, neuropathy (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity \[FACT/GOG-NTX\]), and fatigue quality of life (QOL) by strata. V. To determine the number of patients who proceed to autologous or allogeneic hematopoietic stem cell transplantation (HSCT). VI. To determine the number of patients who successfully undergo stem cell collection among those planning to proceed to autologous HSCT. OUTLINE: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response or partial response at any time after 4 cycles may discontinue study therapy to proceed to autologous or allogeneic stem cell transplant. After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for 3 years.
Investigators
Kristie Blum
Principal Investigator
Emory University
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed classical Hodgkin lymphoma
- •Patients must be 12 years of age or older
- •Patients must have received at least 1-2 prior multi-agent chemotherapy or immunotherapy regimens will be divided into two cohorts based on the following clinical scenarios:
- •Patients enrolled to cohort A must have received only ONE prior brentuximab-containing regimen with NO prior checkpoint inhibitors. Patients enrolled to cohort A must have received brentuximab as part of their first-line treatment regimen.
- •Patients enrolled to cohort B must have received only ONE prior immune checkpoint inhibitor- (i.e. nivolumab or pembrolizumab) containing regimen and NO prior brentuximab. Patients in cohort B may have received an immune checkpoint inhibitor during either their first- or second-line treatment regimen.
- •If radiation is used as part of the planned front-line treatment regimen (i.e., brentuximab vedotin-doxorubicin-vinblastine-dacarbazine \[BV-AVD\] + radiation therapy \[RT\] for bulky stage II disease), this will count as only 1 prior therapy. Additionally, radiation as consolidation after a second-line multi-agent chemotherapy regimen is permitted and will not be counted as a third regimen
- •No prior autologous or allogeneic transplant
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 for patients \> 18 years old, or Lansky performance status of \>= 50 for patients ages 12-18 years
- •Enrolling patients must have measurable disease defined as a tumor or nodal mass \> 1.5 cm in at least one dimension
- •Resolution of all prior toxicities, including peripheral neuropathy, to a =\< grade 1
Exclusion Criteria
- •Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for \>= 2 years or which will not limit survival to \< 2 years
- •Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events to =\< grade 1
- •Active autoimmune disease or history of autoimmune disease such as hepatitis, hypophysitis, nephritis, interstitial lung disease, and colitis
- •Active central nervous system (CNS) involvement with lymphoma
- •Patients with hepatitis B (positive hepatitis B virus surface antigen \[HBsAg\] or hepatitis B virus core antibody \[HBcAb\]) and those with positive hepatitis C virus (HCV) antibodies are not permitted to enroll
- •No active infection, or other active illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Arms & Interventions
Treatment (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response or partial response at any time after 4 cycles may discontinue study therapy to proceed to autologous or allogeneic stem cell transplant.
Intervention: Brentuximab Vedotin
Treatment (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response or partial response at any time after 4 cycles may discontinue study therapy to proceed to autologous or allogeneic stem cell transplant.
Intervention: Hematopoietic Cell Transplantation
Treatment (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response or partial response at any time after 4 cycles may discontinue study therapy to proceed to autologous or allogeneic stem cell transplant.
Intervention: Nivolumab
Treatment (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response or partial response at any time after 4 cycles may discontinue study therapy to proceed to autologous or allogeneic stem cell transplant.
Intervention: Quality-of-Life Assessment
Treatment (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response or partial response at any time after 4 cycles may discontinue study therapy to proceed to autologous or allogeneic stem cell transplant.
Intervention: Questionnaire Administration
Outcomes
Primary Outcomes
Overall response rate (ORR)
Time Frame: Up to 16 cycles (each cycle is 21 days)
Will be calculated and a 95% confidence interval will be estimated using the Clopper-Pearson method. Assessed per Lugano 2014 Criteria at any time point while on study therapy. Will be analyzed independently for each cohort (A and B).
Secondary Outcomes
- Incidence of adverse events(Up to 5 years)
- Incidence of symptomatic toxicity(Up to 5 years)
- Complete response rate (CRR)(Up to 16 cycles (each cycle is 21 days))
- Overall survival (OS)(From time of study enrollment until death from any cause, assessed up to 5 years)
- Progression-free survival (PFS)(From time of study enrollment until first documentation of progressive disease or death from any cause, assessed up to 5 years)