This phase I trial tests the safety, side effects and effectiveness of emapalumab with post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil in preventing graft-versus-host disease (GVHD) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after reduced-intensity donor (allogeneic) hematopoietic cell transplant (HCT). Giving chemotherapy, such as fludarabine, melphalan, or busulfan, before a donor \[peripheral blood stem cell\] transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When healthy stem cells for a donor are infused into a patient (allogeneic HCT), they may help the patient's bone marrow make more healthy cells and platelets. Allogeneic HCT is an established treatment, however, GVHD continues to be a major problem of allogeneic HCT that can complicate therapy. GVHD is a disease caused when cells from a donated stem cell graft attack the normal tissue of the transplant patient. Emapalumab binds to an immune system protein called interferon gamma. This may help lower the body's immune response and reduce inflammation. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill cancer cells. It may also lower the body's immune response. Tacrolimus is a drug used to help reduce the risk of rejection by the body of organ and bone marrow transplants. Mycophenolate mofetil is a drug used to prevent GVHD after organ transplants. It is also being studied in the prevention of GVHD after stem cell transplants for cancer, and in the treatment of some autoimmune disorders. Mycophenolate mofetil is a type of immunosuppressive agent. Giving emapalumab with post-transplant cyclophosphamide, tacrolimus and mycophenolate mofetil may be safe, tolerable and/or effective in preventing GVHD in patients with AML or MDS after a reduced-intensity allogeneic HCT.
Documented informed consent of the participant and/or legally authorized representative
Assent, when appropriate, will be obtained per institutional guidelines
Age: ≥ 18 years and ≤ 75 years
Note: Patients > 70 years of age must have Karnofsky performance status ≥ 80% and HCT-comorbidity index (CI) ≤ 2
Prior allogeneic HCT
FLT3 inhibitors
IDH1/2 inhibitors
Menin inhibitors
Single group
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Busulfan
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo chest CT
Cyclophosphamide
DrugGiven IV
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Emapalumab
Biological/VaccineGiven IV
Fludarabine
DrugGiven IV
Hematopoietic Cell Transplantation
Procedure/SurgeryGiven infusion
Melphalan
DrugGiven IV
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Mycophenolate Mofetil
DrugGiven IV or PO
Questionnaire Administration
Other interventionAncillary studies
Tacrolimus
DrugGiven IV or PO
Incidence of grade 3 or higher adverse events (AEs)
Will be based on Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0, with the exception of infections which ill be graded based on the Report of the Bone Marrow Transplant (BMT) Clinical Trials Network (CTN) Infections Disease Technical Committee. The toxicity/AE information recorded on each subject will include type, severity, duration, and attribution/ association with the study regimen. Tables will be constructed to summarize the observed incidence, severity and type of toxicity, including infection.
Incidence of severe infusion reaction
Will be defined as grade 4 per CTCAE v 5.0 after receiving the first or second dose of emapalumab. The toxicity/AE information recorded on each subject will include type, severity, duration, and attribution/ association with the study regimen. Tables will be constructed to summarize the observed incidence, severity and type of toxicity, including infection.
Incidence of primary graft failure
Will be defined as the failure to achieve an absolute neutrophil count of 500/ul or more for 3 days and donor chimerism of less than 5%. Will be calculated using the competing risk method as described by Gooley et al. (1999).
Non-relapse mortality (NRM)
Will be calculated using the competing risk method as described by Gooley et al. (1999).
Incidence of grade 2-4 acute graft-versus-host-disease (aGVHD)
Will be calculated using the competing risk method as described by Gooley et al. (1999).
Incidence of grade 3 or higher AEs
Will be defined by CTCAE v 5.0 with the exception of infections which will be graded based on the Report of the BMT CTN Infectious Disease Technical Committee. The toxicity/AE information recorded on each subject will include type, severity, duration, and attribution/ association with the study regimen. Tables will be constructed to summarize the observed incidence, severity and type of toxicity, including infection.
Overall survival
Will be calculated using the Kaplan-Meier method.
Progression free survival
Will be calculated using the Kaplan-Meier method.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
