Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT03150329|
Recruitment Status : Recruiting
First Posted : May 12, 2017
Last Update Posted : July 30, 2018
|Condition or disease||Intervention/treatment||Phase|
|Grade 3a Follicular Lymphoma Grade 3b Follicular Lymphoma Recurrent Classical Hodgkin Lymphoma Recurrent Diffuse Large B-Cell Lymphoma Recurrent Follicular Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma Refractory Classical Hodgkin Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Follicular Lymphoma Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma||Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Drug: Vorinostat||Phase 1|
I. To assess the safety and tolerability of vorinostat plus pembrolizumab therapy by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.
II. To determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of vorinostat when given in combination with pembrolizumab.
I. To obtain preliminary estimates of the anti-tumor activity of pembrolizumab plus vorinostat therapy by assessing the overall response rate (ORR), complete response (CR) rate, duration of response (DOR), overall survival (OS) and progression-free survival (PFS).
I. Evaluate responses and disease progression according to the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).
II. Explore genomic biomarkers of response and resistance to pembrolizumab plus vorinostat therapy in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), or Hodgkin lymphoma (HL).
III. Explore immunologic biomarkers of response and resistance to pembrolizumab plus vorinostat therapy in patients with DLBCL, FL, or HL.
IV. Explore the value of circulating DNA (ctDNA) as a biomarker of response to pembrolizumab plus vorinostat therapy.
OUTLINE: This is a dose-escalation study of vorinostat.
Patients receive vorinostat orally (PO) twice a day (BID) on days 1-5 and 8-12 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 days for 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, and then every 12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of Pembrolizumab Plus Vorinostat for Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Hodgkin Lymphoma|
|Actual Study Start Date :||September 1, 2017|
|Estimated Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||July 2019|
Experimental: Treatment (vorinostat, pembrolizumab)
Patients receive vorinostat PO BID on days 1-5 and 8-12 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days for 24 months in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 2 years ]Will be described by type, severity, duration, reversibility, and attribution.
- Complete response rate [ Time Frame: Up to 2 years ]Response rates will be evaluated based on number and type of prior therapy(ies).
- Duration of response [ Time Frame: From the first achievement of partial response or complete response to time of progressive disease assessed up to 2 years ]Will be estimated using the product-limit method of Kaplan and Meier.
- Overall response rate [ Time Frame: Up to 2 years ]Will be calculated as the proportion of evaluable patients that have confirmed CR or PR, as defined according to the 2014 Lugano Classification, exact 95% confidence intervals will be calculated for these estimates. Response rates will also be evaluated based on number and type of prior therapy(ies).
- Overall survival [ Time Frame: From initiation of study therapy to death from any cause assessed up to 2 years ]Will be estimated using the product-limit method of Kaplan and Meier.
- Progression free survival [ Time Frame: From initiation of study therapy to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed up to 2 years ]Will be estimated using the product-limit method of Kaplan and Meier.
- Time to response [ Time Frame: Up to 2 years ]Will be estimated using the product-limit method of Kaplan and Meier.
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): NCT03150329
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Alex F. Herrera, MD 626-256-4673 ext 62405 firstname.lastname@example.org|
|Principal Investigator: Alex F. Herrera, MD|
|United States, New Jersey|
|Hackensack University Medical Center||Recruiting|
|Hackensack, New Jersey, United States, 07601|
|Contact: Tatyana Feldman, MD 551-996-4469 Tatyana.Feldman@hackensackmeridian.org|
|Principal Investigator: Tatyana Feldman, MD|
|Principal Investigator:||Alex Herrera, MD||City of Hope Medical Center|