Pembrolizumab and Vorinostat in Patients With Relapsed or Refractory DLBCL, FCL or HL.
A Phase 1 Study of Pembrolizumab Plus Vorinostat for Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Hodgkin Lymphoma
2 other identifiers
interventional
52
1 country
1
Brief Summary
This phase I trial studies the side effects and best dose of vorinostat when given together with pembrolizumab in treating patients with diffuse large B-cell lymphoma, follicular lymphoma, or Hodgkin lymphoma that has come back after a period of improvement or that does not respond to treatment. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer and may interfere with the ability of cancer cells to grow and spread. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving vorinostat and pembrolizumab together may work better than pembrolizumab alone in treating patients with diffuse large B-cell lymphoma, follicular lymphoma, or Hodgkin lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2017
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 10, 2017
CompletedFirst Posted
Study publicly available on registry
May 12, 2017
CompletedStudy Start
First participant enrolled
July 18, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 23, 2023
CompletedResults Posted
Study results publicly available
February 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2026
ExpectedSeptember 3, 2025
August 1, 2025
5.9 years
May 10, 2017
November 29, 2023
August 18, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
Number of Patients With Grade 3-5 Adverse Events
Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
From initial study treatment to 90 days post-last dose, up to 27 months.
Maximum Tolerated Dose (MTD) on Vorinostat
MTD is defined as the highest dose level at which \< 33% of evaluable subjects experienced DLT, when at least 6 patients were treated at that dose level. The MTD was considered the recommended phase II dose (RP2D), however the principal investigator may ultimately choose a lower dose level as the RP2D, depending on toxicity considerations, dose reduction on subsequent cycles, and other considerations.
From initial study treatment to two cycles of study treatment
Number of Participants With Dose-limiting Toxicities (DLT)
The dose-limiting toxicity (DLT) observation period was 42 days (2 cycles). DLT assessment occurred on cycle 3, day 1 prior to receipt of cycle 3, day 1 of study therapy. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03).
From initial study treatment to two cycles of study treatment, up to 42 days.
Secondary Outcomes (2)
Overall Response Rate (ORR)
From initial study treatment up to 36 21-day cycles
Complete Response Rate (CR)
From the initial treatment to 36 21-day cycles.
Study Arms (2)
Vorinostat 100mg + Pembrolizumab 200mg
EXPERIMENTALPatients receive Vorinostat 100mg PO BID on days 1-5 and 8-12 and pembrolizumab 200mg IV over 30 minutes on day 1. Cycles repeat every 21 days for 24 months in the absence of disease progression or unacceptable toxicity.
Vorinostat 200mg + Pembrolizumab 200mg
EXPERIMENTALPatients receive Vorinostat 200mg PO BID on days 1-5 and 8-12 and pembrolizumab 200mg IV over 30 minutes on day 1. Cycles repeat every 21 days for 24 months in the absence of disease progression or unacceptable toxicity.
Interventions
Correlative studies
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- Have a histologically confirmed diagnosis of follicular lymphoma, diffuse large B-cell lymphoma, or classical Hodgkin lymphoma according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution
- FL: grade 1, 2, 3A, or 3B are eligible
- DBLCL: transformed indolent lymphomas (TIL), primary mediastinal large B-cell lymphoma (PMBCL), and aggressive B-cell lymphoma unclassified (BCL-U) are eligible
- HL: all classical HL subtypes are eligible except for nodular lymphocyte predominant Hodgkin lymphoma, which is excluded
- Patients with HL or DLBCL must refuse or not be candidates for curative autologous stem cell transplantation
- Have relapsed or refractory disease after at least 1 prior regimen, including:
- Recurrence of disease after a documented complete response (CR)
- Progression of disease after a partial response (PR) to the prior regimen
- Partial response (PR), stable disease (SD) or progressive disease (PD) at the completion of the prior treatment regimen; if a patient has PR to prior regimen without PD, there must be biopsy-proven residual disease that is measurable
- Documented informed consent of the participant or legally authorized representative
- Have measurable disease by computed tomography (CT) or positron emission tomography (PET) scan, with one or more sites of disease \>= 1.5 cm in longest dimension
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion prior to starting study therapy or from archival tissue of a biopsy that was performed after the most recent systemic therapy
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Absolute neutrophil count (ANC) \>= 1,000/mcL (within 14 days of treatment initiation)
- Platelets \>= 75,000/mcL (within 14 days of treatment initiation)
- +10 more criteria
You may not qualify if:
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 3 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has received a prior allogeneic hematopoietic stem cell transplant within the past 5 years, requires immunosuppression, or has evidence of active graft-versus-host-disease
- Has received prior autologous hematopoietic stem cell transplant within the last 60 days
- Has a known history of active TB (Bacillus tuberculosis)
- Severe hypersensitivity to pembrolizumab or any of its excipients
- Has had a prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 3 weeks earlier; if a patient has progressive or stable disease to prior regimen, rituximab is allowed up to 2 weeks prior to the initiation of study therapy
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Has taken valproic acid, or another histone deacetylase inhibitor, within 2 weeks prior to study day 1
- Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Has known active central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement; subjects with prior CNS involvement by lymphoma must have remission of the CNS component of the lymphoma; these subjects must have a baseline magnetic resonance imaging (MRI) during screening without evidence of new or enlarging brain lesions and must not have any new or progressive neurologic symptoms
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; a history of hemolytic anemia associated with the lymphoma does not exclude a patient from the study
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Has an active infection requiring systemic therapy
- Has a QT interval corrected for heart rate (QTc) \> 470 ms using the Fridericia formula; if the screening electrocardiogram (ECG) has a QTc \> 470ms, the mean QTc of 3 electrocardiograms (ECGs) can be utilized, but must be \< 470 ms
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
City of Hope Medical Center
Duarte, California, 91010, United States
Related Publications (2)
Godfrey J, Mei M, Chen L, Song JY, Bedell V, Budde E, Armenian S, Puverel S, Nikolaenko L, Chen R, Daniels S, Kennedy N, Peters L, Rosen ST, Forman SJ, Popplewell LL, Kwak LW, Herrera AF. Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma. Haematologica. 2024 Feb 1;109(2):533-542. doi: 10.3324/haematol.2023.283002.
PMID: 37470137DERIVEDMei M, Chen L, Godfrey J, Song J, Egelston C, Puverel S, Budde LE, Armenian S, Nikolaenko L, Nwangwu M, Guo W, Gao L, Lee P, Chen R, Daniels S, Kennedy N, Peters L, Zain J, Rosen S, Forman S, Popplewell L, Kwak L, Herrera AF. Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma refractory to prior PD-1 blockade. Blood. 2023 Oct 19;142(16):1359-1370. doi: 10.1182/blood.2023020485.
PMID: 37339586DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Alex Herrera
- Organization
- City of Hope Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Alex F Herrera
City of Hope Medical Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 10, 2017
First Posted
May 12, 2017
Study Start
July 18, 2017
Primary Completion
June 23, 2023
Study Completion (Estimated)
July 1, 2026
Last Updated
September 3, 2025
Results First Posted
February 1, 2024
Record last verified: 2025-08