Nivolumab, Ipilimumab, and Immunotransplant in Treating Participants with Relapsed or Refractory Diffuse Large B Cell Lymphoma

Inclusion Criteria

• Patient must have known pathologic diagnosis of diffuse large B cell lymphoma (DLBCL), and evidence of persistent disease on PET/CT or CT.
• Have pathologically confirmed DLBCL on biopsy
• Be willing and able to provide written informed consent/assent for the trial
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Patients with cytopenias attributable to bone marrow lymphomatous bone marrow involvement per current bone marrow biopsy may be enrolled if other inclusion criteria are met
• Absolute neutrophil count (ANC) >= 1,000 /mcL (within 14 days of treatment initiation)
• Platelets >= 25,000 /mcL (within 14 days of treatment initiation)
• Hemoglobin >= 8 g/dL (within 14 days of treatment initiation)
• Serum creatinine =< 2.0 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 2.0 X institutional ULN (within 14 days of treatment initiation) * Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels 1.5 ULN (with 14 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (within 14 days of treatment initiation)
• Albumin >= 2.5 mg/dL (within 14 days of treatment initiation)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants (within 14 days of treatment initiation)
• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 14 days of treatment initiation)
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of DCBA; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential must be willing to use an adequate method of contraception; contraception should be used for the course of the study through 120 days after the last dose of study medication * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Male subjects of childbearing potential must agree to use an adequate method of contraception; contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy
• Patients who did not achieve PR or CR as per the Lugano criteria following at least 1 cycle of platinum‐based salvage chemotherapy, or patients not eligible for platinum based therapy or beam induction therapy due to decreased ejection fraction (< 40%)
• Patients whom have undergone previous autologous stem cell transplant, and have recurrent or residual disease are eligible for this trial

Exclusion Criteria

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to ipilimumab or nivolumab or any of their excipients
• Has had a prior anti‐cancer monoclonal antibody (mAb) within 28 days prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 28 days earlier
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent * Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study * Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or lymphomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include lymphomatous meningitis, which is excluded regardless of clinical stability
• Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a systemic treatment; subjects on stable dose of corticosteroids less than or equivalent to 10mg of prednisone daily for more than 3 months may be enrolled, and continue their stable dose through treatment
• Has known history of, or any evidence of active, non‐infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre‐screening or screening visit through 120 days after the last dose of trial treatment (roughly two and a half years after enrollment)
• Human immunodeficiency virus (HIV) positive with detectable viral load, or anyone not on stable anti‐viral (highly active antiretroviral therapy [HAART]) regimen
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• History of allogeneic stem‐cell (or other organ) transplantation
• Has received a live vaccine within 30 days of planned start of study therapy * Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu‐Mist) are live attenuated vaccines, and are not allowed