Emapalumab With Post-Transplant Cyclophosphamide, Tacrolimus and Mycophenolate Mofetil for the Prevention of Graft-versus-Host Disease After Donor Reduced-Intensity Hematopoietic Cell Transplant

NCT06996119 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 23822NCI-2025-03603P30CA033572
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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 (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.

Conditions

Acute Myeloid Leukemia; Graft Versus Host Disease; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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).

  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).

  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)

  At day 100

• Incidence of grade 3 or higher AEs

  From day 29 to day 100

• Overall survival

  From the day of stem cell infusion until death, assessed up to 1 year

• Progression free survival

  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)

  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

Study Arms (1)

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.

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

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Prevention (emapalumab, cyclophosphamide)

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Busilvex, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Prevention (emapalumab, cyclophosphamide)

Computed Tomography PROCEDURE

Undergo chest CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Prevention (emapalumab, cyclophosphamide)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Prevention (emapalumab, cyclophosphamide)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Prevention (emapalumab, cyclophosphamide)

Emapalumab BIOLOGICAL

Given IV

Also known as: Anti-IFN gamma Monoclonal Antibody NI-0501, Anti-IFNg mAb NI-0501, Anti-interferon gamma Monoclonal Antibody NI-0501, Emapalumab-lzsg, Gamifant, NI 0501, NI-0501, NI0501

Prevention (emapalumab, cyclophosphamide)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Prevention (emapalumab, cyclophosphamide)

Hematopoietic Cell Transplantation PROCEDURE

Given infusion

Also known as: HCT, Hematopoietic Stem Cell Infusion, HEMATOPOIETIC STEM CELL TRANSPLANT, Hematopoietic Stem Cell Transplantation, HSCT, SCT, Stem Cell Transplant, stem cell transplantation, Stem Cell Transplantation, NOS

Prevention (emapalumab, cyclophosphamide)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalan for Injection-Hepatic Delivery System, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Prevention (emapalumab, cyclophosphamide)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Prevention (emapalumab, cyclophosphamide)

Mycophenolate Mofetil DRUG

Given IV or PO

Also known as: CellCept, MMF

Prevention (emapalumab, cyclophosphamide)

Questionnaire Administration OTHER

Ancillary studies

Prevention (emapalumab, cyclophosphamide)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, FK-506, FK506, Fujimycin, Hecoria, Prograf, Protopic, Tacforius

Prevention (emapalumab, cyclophosphamide)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Graft vs Host Disease; Myelodysplastic Syndromes

Interventions

Specimen Handling; Busulfan; Cyclophosphamide; Emapalumab; fludarabine; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Melphalan; Mycophenolic Acid; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• Amandeep Salhotra

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: May 30, 2025
• Study Start (Estimated): May 25, 2026
• Primary Completion (Estimated): May 25, 2027
• Study Completion (Estimated): May 25, 2027
• Last Updated: May 30, 2025

Record last verified: 2025-05

Locations

US (1)