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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-16

Study Completion Date

2023-08-07

Brief Summary

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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.

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Detailed Description

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Conditions

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Follicular Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

For the first three patients treated on study therapy, treatment of each subsequent patient will not be allowed until the prior patient has completed Cycle 1. If no unexpected adverse events attributed to the combination therapy are observed, after the third patient completes Cycle 1, treatment initiation may occur without restrictions for the remaining patients.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Personalized tumor vaccine

Intervention Type BIOLOGICAL

* 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.

Poly ICLC

Intervention Type DRUG

-The personalized tumor vaccine will be co-administered with poly-ICLC.

Nivolumab

Intervention Type BIOLOGICAL

-Nivolumab will be administered at a dose of 240 mg intravenously

Peripheral blood draws

Intervention Type PROCEDURE

-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

Leukapheresis

Intervention Type PROCEDURE

* 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.

Rituximab

Intervention Type BIOLOGICAL

-Other anti-CD20 mAb treatment can be used

Biopsy

Intervention Type PROCEDURE

-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)

Interventions

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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.

Intervention Type BIOLOGICAL

Poly ICLC

-The personalized tumor vaccine will be co-administered with poly-ICLC.

Intervention Type DRUG

Nivolumab

-Nivolumab will be administered at a dose of 240 mg intravenously

Intervention Type BIOLOGICAL

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

Intervention Type 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.

Intervention Type PROCEDURE

Rituximab

-Other anti-CD20 mAb treatment can be used

Intervention Type BIOLOGICAL

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)

Intervention Type PROCEDURE

Other Intervention Names

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poly-ICLC Opdivo Rituxan

Eligibility Criteria

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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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No