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

Overview

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.

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

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: February 2, 2023

Interventions

• Drug: Ipilimumab
  • Ipilimumab 3 mg/kg every 3 weeks for 4 doses.

Arms, Groups and Cohorts

• Experimental: Ipilimumab After Stem Cell Transplantation
  • 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.

Clinical Trial Outcome Measures

Primary Measures

• Phase I: Maximum Tolerated Dose of Ipilimumab
  • Time Frame: 1 year
  • 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.
• Phase II: Progression Free Survival (PFS)
  • Time Frame: 2 years
  • criteria of the International Myeloma Working Group

Participating in This Clinical Trial

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: 1. Cardiac: LVEF at rest must be ≥ 50% 2. Hepatic: – < 3x ULN ALT – < 1.5 ULN total serum bilirubin, unless there is congenital benign hyperbilirubinemia. 3. 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 4. 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:. 1. 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. 2. 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)

Gender Eligibility: All

Minimum Age: 21 Years

Maximum Age: 73 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Memorial Sloan Kettering Cancer Center
• Collaborator
  • Bristol-Myers Squibb
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Gunjan Shah, MD, Principal Investigator, Memorial Sloan Kettering Cancer Center