Personalized Tumor Vaccine Strategy and PD-1 Blockade in Patients With Follicular Lymphoma

August 9, 2023 updated by: Washington University School of Medicine

Pilot Study of a Personalized Tumor Vaccine Strategy and PD-1 Blockade in Patients With Follicular Lymphoma

Follicular lymphoma (FL) has a number of effective standard of care therapies; however, FL is not currently considered curable. Therefore, designing well tolerated therapies without cumulative and long-term toxicity is critical. This is a pilot safety and feasibility study that combines a personalized tumor vaccine with nivolumab for the treatment of FL. Patients who demonstrate progression on this study may be treated with rituximab (or another monoclonal antibody against CD20) in addition to vaccine therapy with nivolumab at the discretion of treating physician if clinically indicated.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed follicular lymphoma, grade 1-3a
  • Patients who have relapsed after at least 1 prior anti-lymphoma therapy that include anti-CD20 monoclonal antibody and an alkylator chemotherapy agent, or at least 2 prior anti-lymphoma therapies that include anti-CD20 monoclonal antibody, may be included
  • Anti-CD20 mAb-naïve or anti CD20 mAb-sensitive (defined as progression of FL ≥ 6 months following prior anti-CD20 mAb containing therapy).
  • Presence of measurable disease according to the 2014 Lugano Classification
  • Disease course appropriate for therapy initiation approximately 4-5 months from enrollment per treating physician.
  • Tumor site amenable to a) excisional biopsy or b) approximately 12 core biopsies from lymph node or extranodal site(s) or other site of lymphoma or c) other surgical procedure to provide adequate lymphoma sample for TSMA sequencing and screening.
  • At least 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

  • Normal bone marrow and organ function as defined below:

    • Absolute neutrophil count ≥ 1,000/mcl
    • Platelets ≥ 100,000/mcl
    • Total bilirubin ≤ 1.5 x ULN
    • AST, ALT ≤ 3.0 x ULN
    • Creatinine clearance ≥ 50 mL/min (calculated by the Cockcroft-Gault or via 24-hour urine collection)
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  • Known current or previous histologic transformation from indolent non-Hodgkin lymphoma to diffuse large B-cell lymphoma or other aggressive lymphoma histology.
  • Any anti-lymphoma treatment within 6 months' treatment initiation.
  • Prior therapy with anti-PD-1, PD-L1, or PD-L2 agent.
  • Diagnosis of a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Live vaccine within 30 days prior to treatment initiation.
  • Prior organ allograft or allogeneic transplantation.
  • Known central nervous system (CNS) involvement with lymphoma.
  • Tested positive for hepatitis B surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
  • Known history of HIV or AIDS.
  • History of concurrent malignancy requiring active therapy or prior history of another malignancy within 5 years
  • Active, known, or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in absence of an external trigger.
  • Currently receiving any other investigational agents.
  • A history of allergic reactions or significant toxicity attributed to compounds of similar chemical or biologic composition to anti-CD20 mAbs, anti-PD-1 mAbs, or TLR agonists.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  • Women who are pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of nivolumab.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Nivolumab/Poly-ICLC/Vaccine/+/- Rituximab
  • All cycles are 4 weeks (wks), with nivolumab every 2 wks during Cycles 1-6 & every 4 wks during Cycles 7-12 & vaccine on Cycle 1 Days 1, 4, 8, 15; Cycle 2 Day 1; and then on Day 1 of Cycles 4, 6, 8, 10, 12
  • After 2 cycles, restaging will be performed, & patients with CR, PR, or SD will continue on nivolumab + vaccine. Patients with evidence of PD may initiate anti-CD20 mAb therapy (drug to be determined by the treating physician) weekly for 4 wks during Cycle 3, followed by a dose on Day 1 of every other cycle (Cycles 6, 8, 10, and 12).
  • After 6 cycles, restaging will be performed again, and patients with CR, PR, or SD will continue nivolumab + vaccine. Patients with PD at that time point (but not treated with anti-CD20 mAb therapy thus far on this protocol) will initiate anti-CD20 mAb (drug to be determined by the treating physician) therapy weekly for 4 wks during Cycle 7, followed by a dose Day 1 of Cycles 10 & 12 & 2 additional doses 8 wks apart.
Biological: Personalized tumor vaccine
  • Cycle 12 vaccine administration is optional
  • The peptides comprising the vaccine are reconstituted in up to 4 pools with 5 peptides per pool (A, B, C, and D) . At each vaccination time point, each of the up to four pools will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous injection.
Drug: Poly ICLC
-The personalized tumor vaccine will be co-administered with poly-ICLC.
Other Names:
  • poly-ICLC
Biological: Nivolumab
-Nivolumab will be administered at a dose of 240 mg intravenously
Other Names:
  • Opdivo
Procedure: Peripheral blood draws
-Time of biopsy, during the pre-treatment check (any time before cycle 1 day 1), Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, Cycle 12 Day 1, Time of response, and Time of progression or relapse
Procedure: Leukapheresis
  • Prior to the initiation of treatment and up to five days prior to treatment on cycle 6 day 1, patients will undergo apheresis according to standard institutional procedures for non-mobilized collection.
  • Peripheral blood leukocytes will be cryopreserved for later assessment for the presence of T-cells that recognize tumor specific mutant antigens and immunophenotype, and the presence of other lymphocytes or regulatory populations.
Biological: Rituximab
-Other anti-CD20 mAb treatment can be used
Other Names:
  • Rituxan
Procedure: Biopsy
-Biopsies on lymph node or extranodal site(s) are to be obtained at: screening (only after the patient is deemed eligible; during cycle 2 (after treatment on C2D15 and prior to treatment on C3D1); disease relapse or progression (if this occurs)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Feasibility and safety of vaccine in combination with nivolumab +/1 anti-CD20 monoclonal antibody therapy as measured by the number of participants whose personal vaccines can be manufactured and delivered without unacceptable toxicity
Time Frame: Through 6 months following the first treatment of the last patient enrolled (approximately 54 months)
-Unacceptable toxicity will be described as inability to receive further therapy due to toxicities of therapy as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or the occurrence of other toxicities deemed to be at sufficiently high risk to patients by the principal investigator
Through 6 months following the first treatment of the last patient enrolled (approximately 54 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: Through 5 years after completion of treatment (approximately 111 months)
  • ORR = number of participants with complete response + number of participants with partial response
  • Overall response rates will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment
Through 5 years after completion of treatment (approximately 111 months)
Complete response (CR) rate
Time Frame: Through 5 years after completion of treatment (approximately 111 months)
  • CR rates will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment

  • CR:

    • Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
    • London Deauville score of 1 and 2 in lymph nodes and extra lymphatic sites is considered to represent complete metabolic response. A London Deauville score 3 in the post treatment PET scan may be considered to represent complete metabolic response especially if it is not higher than the surrounding normal physiologic uptake.
    • No evidence of FDG avid disease in the bone marrow
    • No new lesions
    • If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy.
Through 5 years after completion of treatment (approximately 111 months)
Duration of response
Time Frame: Through 5 years after completion of treatment (approximately 111 months)
  • Duration of responses will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment
  • Duration of response = time from first vaccine dose to first evidence of disease progression in participants with at least one response of CR, PR, or SD
Through 5 years after completion of treatment (approximately 111 months)
Progression-free survival (PFS)
Time Frame: Through 5 years after completion of treatment (approximately 111 months)
  • PFS will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment
  • PFS: time from first CR, PR, or SD response to disease progression, death, or last follow-up

  • PD:

    • London Deauville score of 4 or 5 in individual target nodes/masses with an increase in intensity of uptake from the baseline and/or new FDG avid foci consistent with lymphoma at interim or end of treatment assessment
    • New FDG avid foci of extranodal disease consistent with lymphoma. If there is concern regarding the etiology of the new lesions, biopsy or interval scan may be considered.
    • New or recurrent FDG avid foci in the bone marrow
Through 5 years after completion of treatment (approximately 111 months)
Overall survival (OS)
Time Frame: Through 5 years after completion of treatment (approximately 111 months)
  • OS will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment
  • OS: time from first vaccine dose to death or last follow-up
Through 5 years after completion of treatment (approximately 111 months)
Partial response (PR) rate
Time Frame: Through 5 years after completion of treatment (approximately 111 months)
  • Partial response rates will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment

  • PR:

    • London Deauville score of 4 or 5 in lymph nodes and extra lymphatic sites with reduced uptake compared with the baseline and residual mass(es) of any size on interim scan
    • Residual bone marrow uptake higher than the uptake in the normal marrow but reduced when compared with baseline If there are persistent focal changes in the marrow in the context of a nodal response consideration should be given to further evaluation with MRI or biopsy or an interval scan
    • No new lesions
Through 5 years after completion of treatment (approximately 111 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Nancy Bartlett, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 16, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 24, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 7, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 17, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 20, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 14, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 9, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201804151

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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