NCT06996119 · City of Hope Medical Center
Emapalumab With Post-Transplant Cyclophosphamide, Tacrolimus and Mycophenolate Mofetil for the Prevention of Graft-versus-Host Disease After Donor Reduced-Intensity Hematopoietic Cell Transplant
What this study is about
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).
View original scientific description
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.
Interventions
PROCEDURE
Biospecimen Collection
Undergo blood sample collection
DRUG
Busulfan
Given IV
PROCEDURE
Computed Tomography
Undergo chest CT
DRUG
Cyclophosphamide
Given IV
PROCEDURE
Echocardiography Test
Undergo ECHO
BIOLOGICAL
Emapalumab
Given IV
DRUG
Fludarabine
Given IV
PROCEDURE
Hematopoietic Cell Transplantation
Given infusion
DRUG
Melphalan
Given IV
PROCEDURE
Multigated Acquisition Scan
Undergo MUGA
DRUG
Mycophenolate Mofetil
Given IV or PO
OTHER
Questionnaire Administration
Ancillary studies
DRUG
Tacrolimus
Given IV or PO
Primary outcome measures
Incidence of grade 3 or higher adverse events (AEs)
Time frame: 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
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
Time frame: From starting the first emapalumab dose to the first observation of a PSE event or day 28 post-HCT, whichever comes first
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
Time frame: From starting the first emapalumab dose to the first observation of a PSE event or day 28 post-HCT, whichever comes first
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)
Time frame: From starting the first emapalumab dose to the first observation of a PSE event or day 28 post-HCT, whichever comes first
Will be calculated using the competing risk method as described by Gooley et al. (1999).
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
- Duarte, California
Collaborators
National Cancer Institute (NCI)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 1, 2026 · Source of record for eligibility and locations