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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04635735

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Locations

Arm

35.6

Anticipated Duration (Months)

6.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory Multiple Myeloma	Drug: Ipilimumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a phase I/II, single arm, open label trial.This is a phase I/II, single arm, open label trial.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 12, 2020

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: Ipilimumab Ipilimumab 3 mg/kg every 3 weeks for 4 doses.

Arm

Intervention/Treatment

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.

Drug: Ipilimumab

Ipilimumab 3 mg/kg every 3 weeks for 4 doses.

Outcome Measures

Primary Outcome Measures

Phase I: maximum tolerated dose of Ipilimumab [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) [2 years]
criteria of the International Myeloma Working Group

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 73 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack (Limited Protocol Activities)	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York	United States	11553