Tumor Associated Antigen Specific T Cells (TAA-T) With PD1 Inhibitor for Lymphoma

The investigators will collect blood from the patients to isolate peripheral blood
mononuclear cells. The investigators will then make special cells called dendritic cells to
stimulate the T cells. Then they will add special mixtures of tumor proteins WT1, PRAME and
Survivin and provide a cytokine milieu favorable to T cell expansion/activation, inducing
selective expansion of T cells targeted to kill tumor cells. This process trains the T cells
to recognize the tumor proteins and become specialized TAA-T cells. The cells will be grown
and frozen until ready for us.

While the T cells are growing, the patients will receive 4 doses of Nivolumab given every 2
weeks. Patients will then receive two infusions of the TAA-T cells every two weeks and
monitored for side effects. Patients will not receive any Nivolumab during the 45 days safety
monitoring period from the first infusion. They will then receive additional two doses of
Nivolumab following second TAA-T cell infusion on Days 108 and 122 from starting treatment.

Patient may receive additional doses of TAA-T cells if available and do not have > grade 2
toxicity attributed to TAA-T cells and have stable disease or response. Patients can continue
Nivolumab after Day 136 at the discretion of the referring/treating physician.

This study will first enroll 6 patients total (Groups A and B) in the initial safety
monitoring or DLT group prior to the expansion phase (additional 12 patients in the expansion
cohort). After the initial safety phase is complete, additional 12 patients will be enrolled
to maximum 18 patients.

For Group A Patients: Study treatment will begin any time > 1 week after previous therapy for
relapsed disease.

For Group B Patients (post auto-HSCT): Study treatment will begin any time after neutrophil
engraftment or Day 30 post auto-HSCT whichever comes first.

Both TAA-T cells and Nivolumab will be given at fixed dose with allowed dose de-escalation of
both agents as follows:

TAA-T cell dose: 2 x 107 cells/m2 Nivolumab 3 mg/kg/dose every 2 weeks

From the first 2 enrolled patients, if at least one patient meets dose limiting toxicity
criteria at the above mentioned combination dose level, then the next 2 patients will receive
TAA-T cells at 1 x 107 cells/m2 without a change in nivolumab dose. If toxicity criteria are
met by at least one patient from these 2 patients, then the dose of Nivolumab will be reduced
to 1mg/kg/dose for next 2 patients and T cells will be given at the same de-escalated dose of
1x 107 cells/m2.

If patient meets eligibility criteria for TAA-T cell infusion (stable disease, response or
non-life threatening progression), the patient will receive two TAA-T cell infusions given 2
weeks apart, where the expected volume of infusion is 1 to 10 cc.

In case the patient experiences dose limiting toxicity (DLT) from nivolumab prior to the
first TAA-T cell infusion, they can receive the TAA-T cells after resolution of the Nivolumab
toxicities and steroid dosing has been reduced less than 0.5mg/kg/day.

Inclusion Criteria:

Group A (patients with measurable disease) Relapsed/Refractory Hodgkin Lymphoma (HL) and
Diffuse Large B cell Lymphoma (DLBCL) DLBCL

- Patients with Primary Treatment Failure (PTF) and one or more Ultra-high risk (UHR)
features, no prior salvage treatment required (justification for including these
patients even without a salvage regimen is included below). Please refer to Appendix
A.

- Rel/ref DLBCL failing (relapsing after or with inadequate response to) 1st salvage
with tertiary International Prognostic Index (IPI) ≥ 2 (IPI prior to 3rd line
treatment). Please refer to Appendix A for IPI scoring.

- Rel/ref failing 1st salvage deemed unsuitable for 2nd salvage checkpoint inhibitor
therapy (CIT)

- Rel/ref with inadequate response to 2 or more salvage regimens, thus ineligible for
hematopoietic stem cell transplant (HSCT) HL

- Rel/ref ineligible for salvage HL

- Rel/ref HL failing ≥ 2 salvage regimens, including prior Brentuximab Vedotin (BV) and
checkpoint inhibitor therapy

- Rel/ref after autologous BMT and post-transplant Brentuximab vedotin (BV) Checkpoint
inhibitory therapy, if eligible to receive these

Group B (consolidation after auto-HSCT for patients at high risk for relapse) DLBCL only

- Patients with at least one UHR feature at relapse

- Patients with PR (by PET/CT) prior to autologous HSCT)

- Patients with SD/PD (by PET/CT) prior to autologous HSCT

Recipient procurement (TAA-T cell generation) inclusion criteria

- Evidence of HL or DLBCL by morphology, PET/CT uptake in a site of previous disease in
the absence of other etiologies

- Age 12 years to 80 years

- Karnofsky/Lansky score of ≥ 50 (see appendix C).

- Agree to use contraceptive measures during study protocol participation (when age
appropriate)

- Patient or parent/guardian capable of providing informed consent

Recipient inclusion criteria for initial and subsequent TAA-T cell infusion

- Evidence of HL or NHL by morphology, PET/CT uptake in a site of previous disease in
the absence of other etiologies

- Age 12 years to 80 years

- Steroids less than 0.5 mg/kg/day prednisone or equivalent

- Karnofsky/Lansky score of ≥ 50

- Pulse oximetry of > 90% on room air

- Bilirubin ≤ 2.5 mg/dL, AST/ALT ≤ 5x upper limit of normal, serum creatinine < 1.0 or
2x the upper limit of normal (whichever is higher)

- Absolute neutrophil count > 250/µL (may be supported with GCSF)

- Agree to use contraceptive measures during study protocol participation (when age
appropriate)

- Patient or parent/guardian capable of providing informed consent

- LVEF > 50% or LVSF > 27% if history of TBI > 500 cGy

Exclusion Criteria:

- Recipient procurement (TAA-T cell generation) exclusion criteria

- Prior allogeneic BMT

- Patients with uncontrolled infections

- Patients with active HIV

- Pregnancy or lactating

- Active signs of autoimmunity including pancreatitis, diarrhea, hypophysitis

- Patients receiving ATG, Campath or other immunosuppressive T cell monoclonal
antibodies within 28 days of screening for enrollment Recipient exclusion criteria for
initial and subsequent TAA-T cell infusion

- Investigational therapies within the last 28 days

- Uncontrolled infections