Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Follicular

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Gastrointestinal Agents

Nivolumab

Vaccines

Rituximab

Poly ICLC

Complement C3

Complement C3d

Poly I-C

Carboxymethylcellulose Sodium

Antineoplastic Agents, Immunological

Immunologic Factors

Immune Checkpoint Inhibitors

Interferons

Laxatives

Cathartics

Antiviral Agents

* 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.

* 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.

Personalized tumor vaccine

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

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

-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

Peripheral blood draws

* 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.

Leukapheresis

-Other anti-CD20 mAb treatment can be used

-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)

Biopsy

Nancy Bartlett, M.D.

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.

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.

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

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

-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

* 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

* 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.

* 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

* 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

* 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

* 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

Spots Global Cancer Trial Database for personalized tumor vaccine