Phase I Study Utilizing Tumor Associated Antigen Specific T Cells (TAA-T) With PD1 Inhibitor Nivolumab for Relapsed/Refractory Lymphoma
This is a Phase I, open-label multi-site trial designed to evaluate the safety of administering rapidly-generated Tumor associated antigen specific T cells (TAA-T) with the Programmed Death1 (PD-1) inhibitor Nivolumab, in relapsed/refractory lymphoma (rel/ref) patients with measurable disease (group A) or as adjunctive therapy following autologous hematopoeitic stem cell transplant(HSCT) for patients at high risk of relapse (group B). The purpose of this study is to find out if the tumor specific T cells given with Nivolumab are safe and to learn what the side effects are and if the combination can help patients with relapsed lymphomas.
⁃ Group A (patients with measurable disease) Relapsed/Refractory Hodgkin Lymphoma (HL) and Diffuse Large B cell Lymphoma (DLBCL) DLBCL
• Patients who have failed at least 2 lines of prior therapy with a failed attempt at both an autologous stem cell transplant and chimeric antigen receptor T cell therapy.
• Patients who are deemed autologous stem cell transplant ineligible and have failed only one line of prior therapy.
• Systemic therapies to treat prior indolent lymphomas count towards previous DLBCL lines of therapy unless the treatment was anti-CD20 antibody monotherapy.
⁃ HL
• Rel/ref HL failing more than or equal to 1 salvage regimens, including prior Brentuximab Vedotin (BV)
• Rel/ref after autologous HSCT
⁃ Group B (consolidation after auto-HSCT for patients at high risk for relapse) DLBCL
• Patients with \< CMR/CR (by PET/CT) with initial treatment regimen
• Patients with relapse \<12 months from diagnosis or \<6 months from completion of initial therapy
• Patients with \<CMR/CR (by PET/CT) prior to autologous HSCT
• Patients requiring \>1 salvage regimen prior to autologous HSCT HL
• Patients with relapse \<12 months from diagnosis or \<6 months from completion of initial therapy
• Patients with \<CMR/CR (by PET/CT) prior to autologous HSCT
• Patients requiring \>1 salvage regimen prior to autologous HSCT
• Age \>12 years
• Karnofsky/Lansky score of more than or equal to 50 (see appendix C).
• ALC \> 600
• Patients receiving Granulocyte colony-stimulating factor (G-CSF) are recommended a washout period of a minimum of two weeks before procurement
• Agree to use contraceptive measures during study protocol participation (when age appropriate)
• Patient or parent/guardian capable of providing informed consent
• Age \>12 years
• Patient has received at least 8 weeks of Nivolumab
• Patients with Grade 1 toxicities attributed to Nivolumab will be eligible at the discretion of the PI. Toxicities include but not limited to: laboratory abnormalities in thyroid function tests suggestive of hypothyroidism, thyroiditis or thyroid dysfunction adequately managed with thyroid hormone replacement, or abnormalities in amylase, lipase
• Steroids less than 0.5 mg/kg/day prednisone or equivalent
• Karnofsky/Lansky score of more than or equal to 50
• Pulse oximetry of \> 90% on room air
• Bilirubin less than or equal to 2.5 mg/dL, AST/ALT less than or equal to 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