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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a drug called emapalumab can safely prevent graft-versus-host disease (GVHD) in individuals with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) following a specific type of stem cell transplant. GVHD occurs when donor cells attack the body, causing complications. Emapalumab, combined with other medications, may reduce this risk. Individuals with AML or MDS planning a certain type of stem cell transplant might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, other cancer therapies are not allowed within two weeks of starting the transplant conditioning, except for certain targeted agents that can be continued up to one day before conditioning.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found emapalumab to be safe, showing no increased risk of side effects compared to other treatments. When tested in patients with immune system issues, it was generally well-tolerated. Although some serious infections occurred, they were rare.

The other drugs in this trial—cyclophosphamide, tacrolimus, and mycophenolate mofetil—already assist with transplants. They can cause side effects, but doctors usually manage these effectively.

Overall, emapalumab and the other drugs have been used safely in various situations. This suggests they may be safe together for preventing graft-versus-host disease (GVHD), but further research is needed to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about emapalumab for graft-versus-host disease (GVHD) because it works differently from standard treatments. Most current treatments focus on broadly suppressing the immune system to prevent it from attacking the host. Emapalumab, on the other hand, specifically targets and neutralizes interferon gamma, a key player in the inflammatory process of GVHD. This targeted action could mean more effective control of the disease with potentially fewer side effects. Additionally, emapalumab is administered intravenously, allowing for precise dosing and monitoring.

What evidence suggests that this trial's treatments could be effective for preventing GVHD?

Research suggests that emapalumab, which participants in this trial may receive, might help prevent graft-versus-host disease (GVHD) by calming the body's immune response. Emapalumab targets a protein called interferon gamma, which plays a role in inflammation. Previous studies on conditions like hemophagocytic lymphohistiocytosis (HLH) have shown that emapalumab can reduce transplant-related complications. For example, it helped lower the risk of issues like mixed chimerism, where donor and patient cells don't mix well, and graft failure, where the transplant doesn't succeed. While specific data for preventing GVHD is still being gathered, these early findings indicate potential benefits in managing the immune response after transplants. ^{2 6 7 8 9}

Who Is on the Research Team?

Amandeep Salhotra

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. ashpublications.org ashpublications.org/blood/article/144/25/2625/517584/Emapalumab-therapy-for-hemophagocytic

Emapalumab therapy for hemophagocytic lymphohistiocytosis ... 39). We show that the use of emapalumab for HLH before HSCT mitigates the risk of mixed chimerism and graft failure after RIC-HSCT.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38429096/

Real-world treatment patterns and outcomes in patients ... Twelve-month survival probability from emapalumab initiation for the entire cohort (N = 46) was 73.1%. There were no discontinuations because of ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124023024

Emapalumab therapy for hemophagocytic ... 39). We show that the use of emapalumab for HLH before HSCT mitigates the risk of mixed chimerism and graft failure after RIC-HSCT.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1911326

Emapalumab in Children with Primary Hemophagocytic ... In the previously treated group, 70% of the patients were able to proceed to transplantation, as were 65% of the patients who received ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04731298

NCT04731298 | Study to Investigate the Pharmacokinetics, ... This study is designed as an open-label, single arm, proof of concept study in order to determine the appropriate emapalumab dosing regimen neutralizing IFNγ ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123077777

Emapalumab, a Fully Human Anti-Interferon Gamma ... Emapalumab has demonstrated efficacy in patients with pHLH and has a favorable safety profile with no increase in the risk of adverse events (AEs), including ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02069899

NCT02069899 | A Study for Long-term Follow-up of ... The aim of this study is to monitor the long-term safety profile of emapalumab in participants who have previously received at least one dose of emapalumab.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10049777/

Successful use of emapalumab in refractory hemophagocytic ... Long-term outcomes of the HLH-2004 study showed improved 5-year survival rates compared with the HLH-94 protocol. The HLH-2004 protocol actually ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/761107Orig1s000MultidisciplineR.pdf

761107Orig1s000 - accessdata.fda.gov incidence of acute and chronic graft versus host disease). Safety: Incidence and seriousness of AEs. Treatment until. HSCT or until. HLH disease.