Testing Nivolumab as a Potential Targeted Treatment in Cancers With Mismatch Repair Deficiency (MATCH-Subprotocol Z1D)
Condition: Advanced Lymphoma; Advanced Malignant Solid Neoplasm; Hematopoietic and Lymphoid Cell Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Plasma Cell Myeloma
MeSH terms: Lymphoma; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Nivolumab
Intervention description: Given IV
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Nivolumab; Lymphoma; Mismatch repair deficiency

Summary:

      This phase II MATCH treatment trial identifies the effects of nivolumab in patients whose
      cancer has a genetic change called mismatch repair deficiency. Mismatch repair deficiency
      refers to cells that have mutations (changes) in certain genes that are involved in
      correcting mistakes made when DNA is copied in a cell. Immunotherapy with monoclonal
      antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may
      interfere with the ability of cancer cells with mismatch repair deficiency to grow and
      spread. Researchers hope to learn if nivolumab will shrink this type of cancer or stop its
      growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have met applicable eligibility criteria in the Master MATCH Protocol
             prior to registration to treatment subprotocol

          -  Patients must have mismatch repair deficiency as determined via the MATCH Master
             Protocol

          -  Women of childbearing potential (WOCBP) receiving nivolumab must agree to use adequate
             contraception (hormonal or double barrier method of birth control; abstinence) from
             one week prior to study treatment starting, during treatment, and for a period of 5
             months after the last dose of nivolumab. Men receiving nivolumab and who are sexually
             active with WOCBP must agree to use adequate contraception (hormonal or double barrier
             method of birth control; abstinence) from one week prior to study treatment starting,
             during treatment, and for a period of 7 months after the last dose of nivolumab

          -  Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection may be
             eligible provided they have the following:

               -  There must be no evidence of clinically significant hepatic injury from hepatitis
                  virus infection

               -  For HBV, patients must be on suppressive therapy and have undetectable HBV viral
                  load

               -  For HCV, patients must either be on suppressive therapy for HCV or have already
                  completed therapy thought to have eradicated HCV

        Exclusion Criteria:

          -  Patients must not have known hypersensitivity to nivolumab or compounds of similar
             chemical or biologic composition

          -  No prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,
             anti-CD40 or anti-CTLA-4 antibodies (or any other antibody targeting T cell
             co-regulatory pathways)

          -  Patients with cancers for which nivolumab is approved or becomes approved are excluded
             (e.g: colorectal cancer, locally advanced or metastatic urothelial carcinoma,
             unresectable or metastatic melanoma, metastatic non-small cell lung cancer, advanced
             renal cell carcinoma, classical Hodgkin lymphoma, and recurrent or metastatic squamous
             cancer of the head and neck)

          -  Must not have received any of the following therapies within four weeks prior to the
             first dose of the study drug: IL-2, interferon, or other non-study immunotherapy
             regimens or immunosuppressive agents

          -  Must not have a history of toxic epidermal necrolysis (Stevens-Johnson syndrome)

          -  Must not have received growth factors, including but not limited to granulocyte-colony
             stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF),
             erythropoietin, etc. within 2 weeks of study drug administration. Use of such agents
             while on study is also prohibited. Prior use of growth factors should be documented in
             the patient's medical history

          -  Must not have a history of any autoimmune disease: inflammatory bowel disease,
             (including ulcerative colitis and Crohn's disease), rheumatoid arthritis, systemic
             progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune
             vasculitis (e.g., Wegener's Granulomatosis), central nervous system (CNS) or motor
             neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre syndrome,
             myasthenia gravis, multiple sclerosis). Patients 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
             (precipitating event). Entry of patients with autoimmune diagnoses not listed here
             must be approved by the protocol chair

          -  Must not be on supplemental home oxygen

          -  Must not have evidence of interstitial lung disease

          -  Patients with a requirement for steroid treatment or other immunosuppressive
             treatment: Patients will be excluded if they have a condition requiring systemic
             treatment with either corticosteroids (> 10 mg daily prednisone equivalents) 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

          -  No history of severe hypersensitivity reaction to any monoclonal antibody