Emapalumab for Graft-versus-Host Disease

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Chemotherapy, Radiation, Biologics, others

Disqualifiers: Prior allogeneic HCT, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 100

15 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Amandeep Salhotra

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for patients with acute myeloid leukemia or myelodysplastic syndrome who are undergoing reduced-intensity donor hematopoietic cell transplant. It aims to prevent graft-versus-host disease, a condition where donated cells attack the patient's body.

Inclusion Criteria

Left ventricular ejection fraction (LVEF) ≥ 50%

I am between 18 and 75 years old.

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent

I do not have any uncontrolled serious illnesses.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplant Conditioning

Participants receive fludarabine and melphalan or busulfan to prepare for hematopoietic cell transplantation

7 days

Daily visits for IV administration

Transplantation and Initial Treatment

Participants receive hematopoietic cell transplantation and initial doses of emapalumab, cyclophosphamide, tacrolimus, and mycophenolate mofetil

28 days

Frequent visits for monitoring and drug administration

Extended Treatment

Continued administration of tacrolimus and mycophenolate mofetil, with monitoring for GVHD and other outcomes

95 days

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes post-transplant

1 year

Follow-up visits at 100 days, 6 months, and 1 year

Treatment Details

Interventions

• Cyclophosphamide
• Emapalumab
• Mycophenolate Mofetil
• Tacrolimus

Trial Overview The safety and effectiveness of emapalumab combined with post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil are being tested. These medications may reduce immune response and inflammation to prevent GVHD after stem cell transplants.

Participant Groups

Group I: Prevention (emapalumab, cyclophosphamide) Experimental Treatment 13 Interventions

Patients receive fludarabine IV on days -7 to -3 and melphalan IV over 1 hour on day -2 or busulfan IV on days -7 and -6 and fludarabine IV on days -7 to -2. Patients receive HCT infusion on day 0 per institutional standards of practice. Patients also receive emapalumab IV over 1 hour on days -8. -1, -7, 14 and 21, cyclophosphamide IV on days 3 and 4, tacrolimus IV or PO on days 5-95, mycophenolate mofetil IV or PO on days 5-35. Additionally, patients undergo chest CT and ECHO or MUGA at baseline and blood sample collection throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+