Study of Ipilimumab after Stem Cell Transplantation in Patients with Relapsed/Refractory Multiple Myeloma

Inclusion Criteria

• INCLUSION CRITERIA PRIOR TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLOHSCT)
• Willing and able to participate as a research subject and provide informed consent (Note: an legally authorized representative [LAR] may sign the consent form on the participant’s behalf)
• Diagnosis of relapsed refractory multiple myeloma defined as more than 2 lines of prior therapy with at least a very good partial remission to most recent salvage therapy * Patients should have Revised Multiple Myeloma International Staging System (R-ISS) stage II or III disease at diagnosis or high risk cytogenetics by International Myeloma Working Group (IMWG) criteria (t(4;14), del(17/17p), t(14;16), t(14;20), nonhyperdiploidy, and gain(1q)) at any time since diagnosis * Note: A line of therapy is treatment between diagnosis and progression or between two progressions
• Eligible for CD34-selected HSCT according to Memorial Sloan Kettering Cancer Center (MSKC) adult bone marrow transplant (BMT) guidelines
• Have a 10/10 matched donor
• Age >= 21, < 73 years
• Karnofsky (adult) performance status >= 70%
• Left ventricular ejection fraction (LVEF) at rest must be >= 50%
• < 3 x upper limit of normal (ULN) alanine aminotransferase (ALT)
• < 1.5 ULN total serum bilirubin, unless there is congenital benign hyperbilirubinemia
• Serum creatinine < 1.2 mg/dl or if serum creatinine is outside the normal range, then creatinine clearance (CrCl) > 40 ml/min (measured or calculated/estimated) with dose adjustment of fludarabine for < 70ml/min
• Diffusion capacity of the lung for carbon monoxide (DLCO) > 50% of predicted (corrected for hemoglobin)
• INCLUSION CRITERIA PRIOR TO IPILIMUMAB
• Non progressive myeloma (partial response or better) as defined by International Myeloma Working Group (IMWG) criteria
• Engraftment of all cell lines without transfusion dependence, defined as * Absolute neutrophil count > 1.0K/mcL x 3 consecutive days * Platelets > 50K/mcL x 7 consecutive days without platelet transfusion * No platelet or red blood cell (RBC) transfusions within the preceding 7 days
• >= 80% donor chimerism in the bone marrow

Exclusion Criteria

• EXCLUSION CRITERIA PRIOR TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLOHSCT)
• Patients ineligible for therapy with ipilimumab, for example:. * Active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone equivalents) or other immunosuppressive medications at enrollment. Inhaled or topical steroids and adrenal replacement doses > 10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease * History of motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre syndrome, myasthenia gravis)
• Female patients who are pregnant or breast-feeding
• Patients with plasma cell leukemia at the time of diagnosis
• Patients who have undergone prior allogeneic hematopoietic stem cell transplantation
• Patients who have had a previous malignancy that is not in remission
• EXCLUSION CRITERIA PRIOR TO IPILIMUMAB
• Active infection or treatment for infection (patients on cytomegalovirus [CMV] therapy will be considered eligible; patients with CMV viremia by polymerase chain reaction [PCR] or disease with end-organ involvement will not be eligible)
• Active GVHD of any grade or prior grade 3-4 GVHD
• Active immune suppression, defined as * Active use of calcineurin inhibitors, mycophenolate mofetil, or other immunomodulators * Steroid dosing exceeding 10 mg/d prednisone or equivalent
• Receiving immunomodulatory agents (ex. thalidomide, lenalidomide, pomalidomide)