Study of Ipilimumab After Stem Cell Transplantation in People With Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This study will test the safety of ipilimumab to see what effects, if any, the drug has when used as maintenance therapy for people with relapsed/refractory multiple myeloma who have received chemotherapy and allogeneic hematopoietic stem cell transplant (AHCT). The investigators also want to find out whether giving ipilimumab after chemotherapy and AHCT is a better way to control the multiple myeloma than chemotherapy and AHCT alone.

Official Title
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A Phase I/II Trial of Ipilimumab After CD34-Selected Allogeneic Stem Cell Transplantation for Patients With Relapsed/Refractory Multiple Myeloma

Conditions
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Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: Ipilimumab


Participation Criteria
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Eligibility Criteria
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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 LAR may sign the consent form on the partipant'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 R-ISS stage II or III disease at diagnosis or high risk cytogenetics by 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 MSKCC adult BMT guidelines. Have a 10/10 matched donor Age ≥ 21, < 73 years. Karnofsky (adult) Performance Status ≥ 70%. Patients must have adequate organ function measured by: Cardiac: LVEF at rest must be ≥ 50% Hepatic: < 3x ULN ALT < 1.5 ULN total serum bilirubin, unless there is congenital benign hyperbilirubinemia. Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated) with dose adjustment of Fludarabine for <70ml/min Pulmonary: 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/mcLx 7 consecutive days without platelet transfusion no platelet or 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 > 10 mg 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 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)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 73 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a phase I/II, single arm, open label trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipilimumab After Stem Cell Transplantation<br>The patient will be admitted to a single room on the Adult Transplantation Service and allogeneic CD34-selected PBSC or marrow transplantation performed as per MSKCC adult BMT guidelines. Patients will be evaluated at approximately day 100 (±2 weeks) after allo-HSCT. | Drug: Ipilimumab<br>* Ipilimumab 3 mg/kg every 3 weeks for 4 doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Maximum Tolerated Dose of Ipilimumab | A maximum of 12 patients will be accrued and DLTs will be assessed in these patients. If any DLT is observed in more than one of the six patient cohort, a lower dose of ipilimumab will be evaluated in a new six patient cohort. | 1 year | 
| Phase II: Progression Free Survival (PFS) | criteria of the International Myeloma Working Group | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ipilimumab, Stem Cell Transplantation, 20-329