Check Point Inhibition After Autologous Stem Cell Transplantation in Patients at High Risk of Post Transplant Recurrence

Inclusion Criteria:

1. Voluntary signed and dated IRB/IEC approved written informed consent form in accordance with regulatory and local guidelines.
2. Be 18 years or older and 80 years or younger on the day of signing consent
3. Have a confirmed diagnosis of:

   * (GROUP A) De novo diffuse large B cell lymphoma that fails to achieve a PET negative complete response to primary rituximab and anthracycline based multi-agent chemotherapy and at least maintains stable disease after salvage chemotherapy or present double/triple hit features defined by overexpression by standard immunohistochemistry of c-MYC plus BCL2 and/or BCL6 or presence of chromosomal translocations as detected by break-apart FISH involving IGH/MYC plus IGH/BCL2 and/or IGH/BCL6 and who only received standard chemoimmunotherapy with rituximab, cyclophosphamide, vincristine and prednisone (R-CHOP) for induction and present at least stable disease after consolidation or salvage chemotherapy. Stable disease (SD) for lymphoma is defined in Appendix B: Lugano Classification for Response Assessment of Non-Hodgkin Lymphoma.
   * (GROUP B) Recurrent high-risk diffuse large B cell lymphoma defined as relapsing within one year of completion of rituximab and anthracycline based multi-agent chemotherapy or a sAAIPI (second-line age-adjusted International Prognostic Index) intermediate or high at relapse or acquisition of double/triple hit features upon relapse (as defined in group A) and at least stable disease after salvage chemotherapy. Patients with an initial diagnosis of low-grade/indolent non-Hodgkin lymphoma (i.e. follicular, marginal zone) who present relapse with histologic transformation to diffuse large B cell lymphoma (confirmed by biopsy) and meet the definition for high-risk as presented above, are also eligible.
   * (GROUP C) De novo high-risk T cell lymphoma with at least stable disease after primary therapy. High risk T cell lymphoma is defined as Stage III or IV disease at presentation and/or failure to achieve CR after frontline chemotherapy. Patients with ALK-positive ALCL will be excluded from the trial. Patients with ALK-negative ALCL in complete response will be excluded from the trial.
   * (GROUP D) Recurrent T cell lymphoma with at least stable disease after salvage therapy. Patients with ALK-positive ALCL will be excluded from the trial.
4. Be deemed eligible for an autologous stem cell transplantation according to the institutional guidelines of the Blood and Marrow Transplantation Program at John Theurer Cancer Center at Hackensack University Medical Center
5. Have an ECOG performance status of 2 or lower
6. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.
7. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential should agree to ongoing pregnancy testing, to be performed prior to each dosing of ipilimumab and nivolumab. See Note below for definition of WOCBP.
8. Women must not be breastfeeding.
9. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab, and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product, even if they have had a vasectomy. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception). See Note below for definition of WOCBP.
10. Females of childbearing potential must be willing to use two methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 2 years. See Note below for definition of WOCBP.
11. Allowable transplant preparative regimens are the following:

    * For non-Hodgkin lymphoma groups (A, B,C,D) BEAM: carmustine 300 mg/m2 day -6, etoposide 200 mg/m2 and cytarabine 200 mg/m2 days -5 to -2, melphalan 140 mg/m2 day -1
    * For Myeloma groups (E and F) Melphalan 200 mg/m2 day -1

Exclusion Criteria:

1. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks 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. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability. Note: Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \> 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
2. Is unable or unwilling to sign informed consent.
3. Has an active, known, or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
4. Patients should be excluded if they have 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. Note: Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \> 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
5. As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
6. Has received an allogeneic stem cell transplant.
7. Has a history of hypersensitivity to nivolumab, ipilimumab, or any of its excipients, or severe hypersensitivity reaction to any previous monoclonal antibody.
8. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to Day 1 of checkpoint inhibitor treatment administration or who has not recovered (i.e., t administration mAb) within 4 weeks prior to dose of trial treatment. Rituximab within that period is allowed.
9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Note: Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \> 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
10. Has known history of, or any evidence of active, non-infectious pneumonitis.
11. Has an active infection requiring intravenous systemic therapy.
12. 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.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
14. 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 23 weeks for females and 31 weeks for males after the last dose of trial treatment.
15. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or known acquired immunodeficiency syndrome (AIDS).
17. Has positive test for Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected) indicating acute or chronic infection, as tested for transplant.
18. Has received a live vaccine within 30 days of planned start of study therapy.