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

Relapsed/Refractory Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04635735
• Other study ID #: 20-329
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: January 12, 2020
• Est. completion date: February 2, 2023

Study information

• Verified date: February 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: February 2, 2023
• Est. primary completion date: February 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 73 Years

Eligibility

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)

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

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

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase II: Progression Free Survival (PFS)	criteria of the International Myeloma Working Group	2 years

External Links

•   Memorial Sloan Kettering Cancer Center