Acute Myeloid LeukemiaPhase 1NCT06996119
Emapalumab With Post-Transplant Cyclophosphamide, Tacrolimus and Mycophenolate Mofetil for the Prevention of Graft-versus-Host Disease After Donor Reduced-Intensity Hematopoietic Cell Transplant
A Phase 1 study testing Biospecimen Collection, Busulfan and Computed Tomography in people with Acute Myeloid Leukemia and Graft Versus Host Disease, run by City of Hope Medical Center at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Myeloid Leukemia, Graft Versus Host Disease, Myelodysplastic Syndrome
- What is being tested?
- Biospecimen Collection, Busulfan and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jun 2026to 25 May 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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-)
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- 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)
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
Amandeep Salhotra, 626-218-2405, asalhotra@coh.org
Amandeep Salhotra
About this study
Official title: Pilot Study of Emapalumab With Post-Transplant Cyclophosphamide as Graft-Versus-Host Disease Prophylaxis for Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation
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.
Read the detailed description
PRIMARY OBJECTIVE:
- Assess the safety and describe the toxicity profile of adding emapalumab to post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis by day 28 post reduced-intensity hematopoietic cell transplantation (HCT).
SECONDARY OBJECTIVES:
- Estimate activity of emapalumab, PTCy, tacrolimus (tacro) and mycophenolate mofetil (MMF) acute GVHD (aGVHD) prophylaxis, by cumulative incidence of aGVHD (grade 2-4) at day +100.
II. Estimate cumulative incidence of chronic GVHD (cGVHD) at 1-year post-HCT. III. Estimate overall survival (OS) and progression-free survival (PFS) at 1- year post-transplant.
IV. Estimate GVHD-free relapse-free survival (GRFS) at 1-year post-HCT. V. Estimate cumulative incidence of relapse/disease progression, and non-relapse mortality (NRM) at day +100 and 1-year post-HCT.
VI. Estimate the rate of grade 2 or higher infection at 100 days. VII. Assess time to engraftment (platelets and neutrophils).
EXPLORATORY OBJECTIVES:
- Evaluate free emapalumab levels by serial blood sampling and assess association with severe aGVHD incidence.
II. Determine levels of interferon gamma (IFNgamma)-related inflammatory cytokines (CXCL-9 and CXCL-10) by serial sampling and assess association with free emapalumab levels and incidence of grade 3-4 aGVHD.
III. aGVHD biomarkers per Mount Sinai Acute GVHD International Consortium (MAGIC) criteria on days + 1, +7, +14 and +28.
IV. Describe the kinetics of immune cell recovery (B, T, natural killer [NK] cells) at days 30, +100, +180 and +365 post-HCT in peripheral blood.
- Evaluate patient quality of life at baseline then on day +100, 6 months, and 1-year post-HCT using patient reported outcomes of Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT).
VI. Obtain a preliminary estimate of gut microbiome diversity at baseline (preferably before fludarabine administration), and then on days +14, +28, +60, and +100 after HCT.
OUTLINE:
Patients receive fludarabine intravenously (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 orally (PO) on days 5-95, mycophenolate mofetil IV or PO on days 5-35. Additionally, patients undergo chest computed tomography (CT) and echocardiography (ECHO) or multigated acquisition scan (MUGA) at baseline and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 100 days after HCT, then at 6 months and 1 year.
- Being tested
- Biospecimen Collection, Busulfan, Computed Tomography, Cyclophosphamide, Echocardiography Test
- Medical subject headings
- Leukemia, Myeloid, Acute, Graft vs Host Disease, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
BusulfanDrug
Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Busilvex, Bussulfam
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo chest CT
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518
Given IV
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
EmapalumabBiological
Also called Anti-IFN gamma Monoclonal Antibody NI-0501, Anti-IFNg mAb NI-0501, Anti-interferon gamma Monoclonal Antibody NI-0501, Emapalumab-lzsg
Given IV
FludarabineDrug
Also called Fluradosa
Given IV
Hematopoietic Cell TransplantationProcedure or surgery
Also called HCT, Hematopoietic Stem Cell Infusion, HEMATOPOIETIC STEM CELL TRANSPLANT, Hematopoietic Stem Cell Transplantation
Given infusion
MelphalanDrug
Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard
Given IV
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA
Also called CellCept, MMF
Given IV or PO
Questionnaire AdministrationOther
Ancillary studies
TacrolimusDrug
Also called FK 506, FK-506, FK506, Fujimycin
Given IV or PO
| Study group | Role | What they receive |
|---|---|---|
| Prevention (emapalumab, cyclophosphamide) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Drug: Busulfan; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography Test; Biological: Emapalumab; Drug: Fludarabine; Procedure: Hematopoietic Cell Transplantation; Drug: Melphalan; Procedure: Multigated Acquisition Scan; Drug: Mycophenolate Mofetil; Other: Questionnaire Administration; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From starting the first emapalumab dose to the first observation of a primary safety endpoint (PSE) event or day 28 post-hematopoietic cell transplantation (HCT), whichever comes first
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.
Measured: From starting the first emapalumab dose to the first observation of a PSE event or day 28 post-HCT, whichever comes first
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).
Measured: From starting the first emapalumab dose to the first observation of a PSE event or day 28 post-HCT, whichever comes first
Non-relapse mortality (NRM)
Will be calculated using the competing risk method as described by Gooley et al. (1999).
Measured: From starting the first emapalumab dose to the first observation of a PSE event or day 28 post-HCT, whichever comes first
Secondary outcomes (12)
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).
Measured: At day 100
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.
Measured: From day 29 to day 100
Overall survival
Will be calculated using the Kaplan-Meier method.
Measured: From the day of stem cell infusion until death, assessed up to 1 year
Progression free survival
Will be calculated using the Kaplan-Meier method.
Measured: From the date of stem cell infusion to the date of death, disease relapse/progression, whichever occurs first, assessed up to 1 year
GVHD relapse-free survival (GRFS)
Will be calculated using the Kaplan-Meier method.
Measured: From the start of HCT to grade III-IV aGVHD, chronic GVHD, requiring systemic treatment, relapse, or death from any cause, whichever occurs first, assessed up to 1 year
Relapse/progression
Will be calculated using the Kaplan-Meier method.
Measured: From day of stem cell infusion (day 0) and at 100 days and at 1 year
NRM
Will be defined as death occurring in a patient from causes other than relapse or progression. 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.
Measured: From date of stem cell infusion until non-disease related death, assessed up to 1 year
Incidence of aGVHD
Will be calculated using the competing risk method as described by Gooley et al. (1999).
Measured: From day 0 (date of stem cell infusion) through 180 days post-transplant
Incidence of chronic GVHD
Will be evaluated and scored according to National Institutes of Health Consensus Staging. Will be calculated using the competing risk method as described by Gooley et al. (1999).
Measured: From day 80 through 1 year post-transplant
Incidence of infection
Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any, according to 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.
Measured: From day -7 to day 100 post-transplant
Absolute neutrophil count recovery
Will be defined as neutrophils >= 0.5 x 10^3/uL achieved and sustained for 3 consecutive lab values on different days with no subsequent decline.
Measured: Up to 1 year
Platelet recovery
Will be defined as platelets >= 20 K/uL independent of platelet transfusion support (date should reflect no transfusions in previous 7 days, and the first of 3 consecutive lab values on different days).
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2025
- Study start12 Jun 2026
- Primary completion25 May 2027 (estimated)
- Study completion25 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Amandeep Salhotra, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06996119
- Sponsor's protocol ID
- 23822
- Other IDs
- NCI-2025-03603, 23822, P30CA033572
- Status last verified
- May 2026
- First submitted
- 21 May 2025
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No