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Grade 3b Follicular LymphomaPhase 1NCT03150329

Pembrolizumab and Vorinostat in Patients With Relapsed or Refractory DLBCL, FCL or HL.

A Phase 1 study testing Laboratory Biomarker Analysis, Pembrolizumab and Vorinostat in people with Grade 3b Follicular Lymphoma and Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between DLBCL and Classic HL, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Pembrolizumab and Vorinostat
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
1 siteUnited States
Study dates
1 Sep 2017to 2 Jun 2027
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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)
  • Hemoglobin >= 8 g/dL without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment (within 14 days of treatment initiation)
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance (CrCl) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (within 14 days of treatment initiation)
  • Serum total bilirubin =< 1.5 x ULN or =< 3 x ULN if patient has Gilberts disease OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (within 14 days of treatment initiation)
  • Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver involvement by lymphoma as the etiology of transaminase elevation (within 14 days of treatment initiation)
  • Albumin >= 2.5 mg/dL (within 14 days of treatment initiation)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 14 days of treatment initiation)
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 14 days of treatment initiation)
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication; Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
  • Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy; Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

Who cannot join

  • 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
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  • 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
  • Is unable to swallow capsules, has a partial or small bowel obstruction, or has a gastrointestinal condition resulting in a malabsorptive syndrome (e.g. small bowel resection with malabsorption)
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy; Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase 1 Study of Pembrolizumab Plus Vorinostat for Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Hodgkin Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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.

SECONDARY OBJECTIVE:

  1. 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).

EXPLORATORY OBJECTIVES:

  1. 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 deoxyribonucleic acid (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 daily (BID) on days 1-5 and 8-12 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles 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.

Being tested
Laboratory Biomarker Analysis, Pembrolizumab, Vorinostat
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • VorinostatDrug

    Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid

    Given PO

Study groups in NCT03150329
Study groupRoleWhat they receive
Vorinostat 100mg + Pembrolizumab 200mgExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Drug: Vorinostat
Vorinostat 200mg + Pembrolizumab 200mgExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Drug: Vorinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients With Grade 3-5 Adverse Events

    Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

    Measured: From initial study treatment to 90 days post-last dose, up to 27 months.

  2. 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.

    Measured: From initial study treatment to two cycles of study treatment

  3. 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).

    Measured: From initial study treatment to two cycles of study treatment, up to 42 days.

Secondary outcomes (2)

  1. Overall Response Rate (ORR)

    ORR was calculated as the proportion of evaluable patients that had confirmed complete response (CR) or partial response (PR), as defined according to the 2014 Lugano Classification, exact 95% confidence intervals were calculated for these estimates.

    Measured: From initial study treatment up to 36 21-day cycles

  2. Complete Response Rate (CR)

    CR was calculated as the proportion of evaluable patients that had confirmed complete response, as defined according to the 2014 Lugano Classification, exact 95% confidence intervals were calculated for these estimates.

    Measured: From the initial treatment to 36 21-day cycles.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2017
  2. Study start1 Sep 2017
  3. Primary completion23 Jun 2023
  4. Study completion2 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03150329
Sponsor's protocol ID
17080
Other IDs
NCI-2017-00800, 17080
Status last verified
Oct 2026
First submitted
10 May 2017
Last updated
3 Nov 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 37470137

  • Mei 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.

    PubMed 37339586

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Pembrolizumab and Vorinostat in people with Grade 3b Follicular Lymphoma and Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between DLBCL and Classic HL, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Grade 3-5 Adverse Events (time frame: From initial study treatment to 90 days post-last dose, up to 27 months.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03150329, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.

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