Nivolumab and Brentuximab Vedotin After Stem Cell Transplant in Treating Patients With Relapsed or Refractory High-Risk Classical Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT03057795|
Recruitment Status : Recruiting
First Posted : February 20, 2017
Last Update Posted : October 31, 2019
|Condition or disease||Intervention/treatment||Phase|
|Classic Hodgkin Lymphoma Hematopoietic Cell Transplant Recipient Recurrent Hodgkin Lymphoma Refractory Hodgkin Lymphoma||Biological: Brentuximab Drug: Brentuximab Vedotin Other: Laboratory Biomarker Analysis Biological: Nivolumab||Phase 2|
I. Assess the efficacy of nivolumab plus brentuximab vedotin consolidation after autologous stem cell transplantation (ASCT) in participants with relapsed/refractory Hodgkin lymphoma (HL), as assessed by 18-month progression-free survival (PFS).
I. Estimate the overall survival (OS), the cumulative incidence of relapse/progression, the cumulative incidence of non-relapse mortality (TRM) in participants with relapsed/ refractory HL who receive nivolumab plus brentuximab vedotin consolidation after ASCT.
II. Estimate the overall response rate to nivolumab plus brentuximab vedotin therapy in participants with measurable disease after ASCT.
III. Establish the safety and tolerability of nivolumab plus brentuximab vedotin when used as consolidation after ASCT in participants with relapsed/ refractory HL.
I. Evaluate the Lymphoma Response to Immunomodulatory therapy Criteria (LYRIC) definition of indeterminate response to guide the management of patients regarding treatment past progressive disease.
II. Explore the impact of nivolumab plus brentuximab vedotin therapy on immune reconstitution after ASCT.
III. Explore the prognostic impact of and temporal dynamics of minimal residual disease (MRD) in the peripheral blood as assessed by the next-generation sequencing-based ClonoSEQ platform.
IV. Explore the prognostic impact of 9p24.1 abnormalities in tumor tissue assessed by fluorescence in situ hybridization (FISH) on outcomes after ASCT and nivolumab plus brentuximab vedotin post-ASCT consolidation therapy.
V. Explore the relationship between immune cells and Hodgkin and Reed/Sternberg (HRS) in tumor samples by 6-color quantitative spatial image analysis using the Vectra system, and correlate with outcome after ASCT and nivolumab plus brentuximab vedotin post-ASCT consolidation therapy.
VI. Explore whether genetic alterations (e.g. gene expression profiles or genetic mutations) in HL tumor samples are associated with outcome after ASCT and nivolumab plus brentuximab vedotin post-ASCT consolidation therapy.
Beginning 30-60 days post-ASCT, 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 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 and 100 days, at 3, 6, 12, and 18 months from start of treatment, and then biannually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||65 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Nivolumab and Brentuximab Vedotin Consolidation After Autologous Stem Cell Transplantation in Patients With High-Risk Classical Hodgkin Lymphoma|
|Actual Study Start Date :||April 3, 2017|
|Estimated Primary Completion Date :||October 8, 2020|
|Estimated Study Completion Date :||October 8, 2020|
Experimental: Treatment (brentuximab vedotin, nivolumab)
Beginning 30-60 days post-ASCT, 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 8 courses in the absence of disease progression or unacceptable toxicity.
Drug: Brentuximab Vedotin
Other: Laboratory Biomarker Analysis
- Progression-free survival [ Time Frame: From the first dose of study treatment to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed at 18 months ]Progression-free survival will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error. When there is no censoring in progression-free survival prior to 18 months after the first dose of study treatment, the observed 18-month progression-free survival will be compared to the baseline of 65% by one-sided exact test of binomial proportion. In case of censoring in progression-free survival prior to 18 months after the first dose of study treatment, the Kaplan-Meier estimate for 18-month progression-free survival along with the Greenwood standard error estimator will be used for the testing of null hypothesis at 65%.
- Overall survival [ Time Frame: From the first dose of study treatment to death from any cause, assessed up to 18 months ]Overall survival will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.
- Cumulative incidence of relapse/progression defined as the time from the first dose of study treatment to disease relapse/progression [ Time Frame: Up to 18 months ]Cumulative incidence of relapse/progression as well as its confidence intervals will be estimated using competing risk methodology, treating the other event as a competing risk.
- Cumulative incidence of non-relapse mortality defined as the time from the first dose of study treatment to non-disease related death [ Time Frame: Up to 18 months ]Cumulative incidence of non-relapse mortality as well as its confidence intervals will be estimated using competing risk methodology, treating the other event as a competing risk.
- Overall response rate [ Time Frame: Up to 18 months ]Overall response rate will be estimated by the proportion of patients achieving either complete response or partial response among participants with measurable disease after autologous stem cell transplantation, along with the exact binomial confidence interval.
- Incidence of toxicities evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 18 months ]Observed toxicities will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03057795
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Alex Herrera 626-256-4673 ext 62405 firstname.lastname@example.org|
|Principal Investigator: Alex Herrera|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Patrick B. Johnston 507-266-4671 email@example.com|
|Principal Investigator: Patrick B. Johnston|
|United States, New Jersey|
|Hackensack University Medical Center||Recruiting|
|Hackensack, New Jersey, United States, 07601|
|Contact: Tatyana A. Feldman 551-996-3033 Tatyana.Feldman@hackensackmeridian.org|
|Principal Investigator: Tatyana A. Feldman|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Not yet recruiting|
|New York, New York, United States, 10065|
|Contact: Gunjan L. Shah firstname.lastname@example.org|
|Principal Investigator: Gunjan L. Shah|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Yago L. Nieto 713-792-8750 email@example.com|
|Principal Investigator: Yago L. Nieto|
|United States, Washington|
|Fred Hutchinson Cancer Research Center||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Leona A. Holmberg 206-667-6447 firstname.lastname@example.org|
|Principal Investigator: Leona A. Holmberg|
|Principal Investigator:||Alex F Herrera||City of Hope Medical Center|