Adding emapalumab to standard post-transplant medicines to prevent graft‑versus‑host disease after reduced‑intensity donor stem cell transplant
Pilot Study of Emapalumab With Post-Transplant Cyclophosphamide as Graft-Versus-Host Disease Prophylaxis for Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation
This trial will test whether adding emapalumab to post‑transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil can prevent graft‑versus‑host disease in adults with AML or MDS receiving a reduced‑intensity donor stem cell transplant.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 15 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | City of Hope Medical Center Academic / other |
| Drugs / interventions | chemotherapy, radiation, fludarabine, emapalumab, cyclophosphamide |
| Locations | 1 site (Duarte, California) |
| Trial ID | NCT06996119 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1 safety trial that gives emapalumab alongside standard post‑transplant graft‑versus‑host disease (GVHD) prophylaxis of post‑transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil after reduced‑intensity conditioning and an 8/8 matched peripheral blood stem cell transplant. Adults with AML or MDS in complete remission and meeting organ and performance criteria are enrolled and receive conditioning with either fludarabine/melphalan or busulfan/fludarabine before the donor graft. The primary goal is to describe safety and toxicity through day +28, with secondary endpoints including acute and chronic GVHD incidence, survival outcomes, relapse and non‑relapse mortality, infection rates, and time to engraftment. Exploratory correlative studies will measure free emapalumab, IFN‑gamma–related cytokines (CXCL9/10), and established GVHD biomarkers to explore pharmacodynamics and associations with severe GVHD.
Who should consider this trial
Good fit: Adults aged 18–75 with AML or MDS in complete remission (bone marrow blasts <5% and AML MRD‑negative), who plan reduced‑intensity conditioning and an 8/8 matched related or unrelated donor peripheral blood stem cell transplant, are eligible.
Not a fit: Patients with active leukemia, MRD‑positive AML, mismatched or alternative donor grafts, or who cannot tolerate required conditioning or immunosuppression are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, adding emapalumab could lower the risk of acute and chronic GVHD after transplant and improve post‑transplant recovery and survival.
How similar studies have performed: Emapalumab is approved for HLH, but using it to prevent GVHD after HCT is a relatively novel application with limited early‑phase clinical data so far.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 * Karnofsky performance status ≥ 70% * Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in complete remission with bone marrow (BM) blast of \< 5%. AML must be negative for minimal residual disease (MRD-) * Planned to undergo reduced-intensity conditioning (RIC) with either fludarabine/melphalan (Flu/Mel) or busulfan/fludarabine (Bu/Flu) regimens prior to an allogeneic HCT using a mobilized peripheral blood stem cell (PBMC) graft from an 8/8 match related/unrelated donor (A, B, C, DR by high resolution typing) * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease) * Aspartate aminotransferase (AST) ≤ 3.0 x ULN * Alanine aminotransferase (ALT) ≤ 3.0 x ULN * Creatinine clearance of ≥ 60 mL/min per 24-hour urine test or the Cockcroft-Gault formula * Left ventricular ejection fraction (LVEF) ≥ 50% * Note: To be performed within 30 days prior to day 1 of protocol therapy * Bazett's correction formula (QTcB) ≤ 480 ms * If able to perform pulmonary function tests: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) (diffusion capacity) ≥ 50% of predicted (corrected for hemoglobin). * If unable to perform pulmonary function tests: Oxygen (O2) saturation \> 92% on room air * Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) OR * If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable * Meets other institutional and federal requirements for infectious disease titer requirements * Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy * QuantiFERON-TB Gold+ * Administer tuberculosis prophylaxis to patients at risk for tuberculosis, or known to have a positive purified protein derivative (PPD) test result, or positive interferon gamma (IFNγ) release assay * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 180 days post-HCT * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) Exclusion Criteria: * Prior allogeneic HCT * Other cancer therapies (chemotherapy, radiation, biologics) are not allowed within two weeks of starting HCT conditioning; however targeted agents for underlying hematologic malignancies may be continued up to one day before conditioning, including, but not limited to: * FLT3 inhibitors * IDH1/2 inhibitors * Menin inhibitors * ABL-BCR inhibitors * BCL-2 inhibitors * Hydroxyurea * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent * Psychological issues, no appropriate caregivers identified, or non-compliant to medication * Clinically significant uncontrolled illness * Active uncontrolled infections (bacterial, viral, fungal). Infections are considered controlled if appropriate therapy has been initiated and, at the time of screening, no signs of infection are present * Other active malignancy * Females only: Pregnant or breastfeeding * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Where this trial is running
Duarte, California
- City of Hope Medical Center — Duarte, California, United States (Recruiting)
Study contacts
- Principal investigator: Amandeep Salhotra — City of Hope Medical Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.