Tildrakizumab for Prevention of Acute Graft-Versus-Host Disease

NCT04112810 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO35737
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2 open-label trial designed to evaluate the efficacy of tildrakizumab in improving graft-versus-host disease (GVHD)-free relapse-free survival after myeloablative allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancy.

Conditions

Hematologic Malignancies

Keywords

Graft-versus-host disease

Outcome Measures

Primary Outcomes (1)

• GVHD-free Relapse-Free Survival

  Number of subjects experiencing any of grade III-IV acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death at 12 months

  1 year

Secondary Outcomes (13)

• Incidence of Chronic GVHD

  Day +180

• Incidence of Chronic GVHD

  Day +365

• Incidence of Acute GVHD

  Day +100 and Day +180

• Incidence of Acute GI GVHD

  Day +100 and Day +180

• Primary Graft Failure.

  Day 28

Study Arms (1)

Tildrakizumab

EXPERIMENTAL

Tildrakizumab (IluymaTM) is a humanized monoclonal antibody that specifically binds to the IL-23p19 subunit of IL-23 to neutralize its function.

Drug: Tildrakizumab

Interventions

Tildrakizumab DRUG

100 mg will be injected subcutaneously on Day -1, Day 28 ± 3, Day 112 ± 7, Day 196 ± 14, and Day 280 ± 14.

Also known as: Iluyma

Tildrakizumab

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Patients with any hematologic malignancy for which alloHCT is indicated. Patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) must be in complete remission at the time of alloHCT (\<5% blasts in the bone marrow, normal maturation of all cellular components in the bone marrow and absence of extramedullary disease). Patients with myelodysplastic syndrome (MDS) must have \<10% blasts in the bone marrow, no circulating blasts.
• Myeloablative conditioning (MAC) regimen, based on Center for International Blood and Marrow Transplant Research (CIBMTR) criteria (total body irradiation (TBI) ≥5 Gy single dose or ≥8 Gy fractionated or busulfan \[Bu\] dose \>8 mg/kg oral or \>6.4 mg/kg intravenous).
• T cell-replete peripheral blood graft.
• Patients must have a matched related or unrelated donor (at least 6/6 match at human leukocyte antigen (HLA) -A, -B and -C for related donors and at least 8/8 match at HLA -A, -B, -C and -DRB1 for unrelated donors).
• Cardiac function: Left ventricular ejection fraction ≥45% for myeloablative conditioning.
• Estimated creatinine clearance ≥40 mL/minute (using the Cockcroft-Gault formula and actual body weight).
• Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% (adjusted for hemoglobin) and forced expiratory volume in 1 second (FEV1) ≥50%.
• Liver function: total bilirubin \<3 x upper limit of normal and alanine aminotransferase (ALT) / aspartate aminotransferase (AST) \<5 x upper normal limit.
• Female subjects must meet one of the following:
• Postmenopausal for at least one year before enrollment, OR
• Surgically sterile (i.e. undergone a hysterectomy or bilateral oophorectomy), OR
• If subject is of childbearing potential (defined as not satisfying either of the above two criteria), she must agree to practice two acceptable methods of contraception (combination methods require use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive) from the time of signing of the informed consent form through 90 days after the last dose of study agent, OR
• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] and withdrawal are not acceptable contraception methods.)
• Male subjects, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:

You may not qualify if:

• Prior allogeneic hematopoietic cell transplant (HCT).
• Active central nervous system (CNS) involvement with malignancy.
• Patients receiving cord blood or haploidentical allograft.
• Patients undergoing in vivo or ex vivo T cell-depleted alloHCT.
• Karnofsky Performance Score \<60% or Eastern Cooperative Oncology Group (ECOG) \> or = 2.
• Patients with uncontrolled bacterial, viral or fungal infections (currently on treatment and with progression of infectious disease or no clinical improvement) at time of enrollment.
• Active hepatitis B or C virus infection or known human immunodeficiency virus (HIV) positive.
• Use of rituximab, alemtuzumab, anti-thymocyte globulin (ATG) or other monoclonal antibody planned as part of conditioning regimen for GVHD prophylaxis.
• Participation in another GVHD prophylaxis clinical trial.
• Any current uncontrolled cardiovascular conditions, including uncontrolled ventricular arrhythmias, New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled angina, or electrocardiographic evidence of active ischemia or active conduction system abnormalities.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Runaas L, Fank S, Palen K, Szabo A, Rein L, Ying G, Salzman N, Samanas L, Abedin SM, Chhabra S, Hamadani M, Longo W, Shah NN, Haber J, Gradissimo A, Waters NR, Peled JU, Johnson B, Kearl T, Drobyski WR. TIDRAKIZUMAB FOR THE PROPHYLAXIS OF GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION. Blood Adv. 2026 Feb 3:bloodadvances.2025019065. doi: 10.1182/bloodadvances.2025019065. Online ahead of print.

  PMID: 41632629 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms; Graft vs Host Disease

Interventions

tildrakizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases

Results Point of Contact

• Title: William R Drobyski, MD, FACP, FASTCT
• Organization: Medical College of Wisconsin

wdrobysk@mcw.edu

414-456-4941

Study Officials

• William Drobyski, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 30, 2019
• First Posted: October 2, 2019
• Study Start: March 1, 2020
• Primary Completion: June 1, 2024
• Study Completion: June 17, 2024
• Last Updated: October 21, 2025
• Results First Posted: July 4, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)