Hematologic MalignanciesPhase 2NCT04112810
Tildrakizumab for Prevention of Acute Graft-Versus-Host Disease
A Phase 2 study testing Tildrakizumab in people with Hematologic Malignancies, run by Medical College of Wisconsin at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancies
- What is being tested?
- Tildrakizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2020to 17 Jun 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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:
- Practice effective barrier contraception during the entire study period and through 60 calendar 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 methods of contraception.)
- Signed informed consent: Voluntary written consent must be given before patient registration and performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
- Planned post-transplant maintenance therapy is allowed.
- Prior autologous transplant is allowed.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: A Phase II Trial of Tildrakizumab for Prevention of Acute Graft-Versus-Host Disease
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.
Read the detailed description
Study Rationale: GVHD remains a major cause of morbidity and mortality following myeloablative conditioning (MAC) alloHCT. Proinflammatory cytokines play a central role in initiation and development of acute GVHD and as such, inhibition of these cytokines has been examined for both prevention and treatment of GVHD. Interleukin (IL)-23 is a proinflammatory cytokine which the investigators' lab has shown to have a unique and selective role in induction of colonic inflammation during acute GVHD and that this cytokine serves as a critical mediator linking conditioning regimen-induced mucosal injury and endotoxin lipopolysaccharide (LPS) translocation to subsequent proinflammatory cytokine production and GVHD-associated pathological damage. Moreover, additional studies have demonstrated that blocking the IL-23 signaling pathway has not abrogated the graft-versus-tumor effect. Tildrakizumab is a commercially available anti-IL-23 antibody FDA approved for the treatment of moderate to severe psoriasis with good tolerance. The investigators hypothesize that blocking IL-23, with tildrakizumab, will reduce GVHD rates for patients undergoing MAC alloHCT without having an impact on relapse rates, thus improving GVHD-free relapse-free survival (GRFS).
- Conditions
- Hematologic Malignancies
- Being tested
- Tildrakizumab
- Keywords
- Graft-versus-host disease
- Medical subject headings
- Hematologic Neoplasms, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TildrakizumabDrug
Also called Iluyma
100 mg will be injected subcutaneously on Day -1, Day 28 ± 3, Day 112 ± 7, Day 196 ± 14, and Day 280 ± 14.
| Study group | Role | What they receive |
|---|---|---|
| Tildrakizumab | Experimental | Tildrakizumab (IluymaTM) is a humanized monoclonal antibody that specifically binds to the IL-23p19 subunit of IL-23 to neutralize its function. Receives: Drug: Tildrakizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 year
Secondary outcomes (13)
Incidence of Chronic GVHD
Number of subjects experiencing chronic GVHD defined by NIH Consensus criteria.
Measured: Day +180
Incidence of Chronic GVHD
Number of subjects experiencing chronic GVHD defined by NIH Consensus criteria.
Measured: Day +365
Incidence of Acute GVHD
Number of subjects experiencing grades II-IV and III-IV acute GVHD will be determined at Day +100 and Day +180 post-HCT. Acute GVHD will be graded according to NIH Consensus criteria.
Measured: Day +100 and Day +180
Incidence of Acute GI GVHD
Number of subjects experiencing grades II-IV and III-IV acute GI GVHD will be determined at Day +100 and Day +180 post-HCT. This will be graded according to NIH Consensus criteria.
Measured: Day +100 and Day +180
Primary Graft Failure.
Number of subjects experiencing no neutrophil recovery to > 500 cells/μL by Day 28 post-HCT.
Measured: Day 28
Secondary Graft Failure
Number of subjects experiencing initial neutrophil engraftment followed by subsequent decline in absolute neutrophil counts <500 cells/μL, unresponsive to growth factor therapy, but cannot be explained by disease relapse or drugs.
Measured: Up to Day 365
Hematopoietic Recovery According to Neutrophil Count Recovery
This measure is the number of subjects with the event. The number of days to hematopoietic recovery will be assessed according to neutrophil count recovery after hematopoietic stem cell transplant (HSCT). Neutrophil recovery or engraftment is defined as achieving an absolute neutrophil count (ANC) ≥500/mm^3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil engraftment.
Measured: Day +28
Hematopoietic Recovery According to Platelet Count Recovery
This measure is the number of subjects with the event. The number of days to hematopoietic recovery will be assessed according to platelet count recovery after HSCT. Platelet recovery is defined by either the first day of a sustained platelet count >20,000/mm^3 for three days with no platelet transfusion in the preceding seven days. The first day of sustained platelet count above these thresholds will be designated the day of platelet engraftment.
Measured: Day +28
Non-relapsed Mortality.
Number of subjects who die after alloHCT without experiencing a relapse.
Measured: Day +100 and 1 year
Disease Relapse or Progression
The number of subjects who experience relapse. Relapse is defined by either morphological, cytogenetic or radiologic evidence of the pretransplant hematologic malignancy.
Measured: Day +100 and 1 year
The Number of Subjects With Progression-free Survival.
This will be measured in months. The event for this endpoint is relapse/progression or death. Patients who are alive and disease-free will be censored at last follow-up.
Measured: Day +100 and 1 year
The Number of Subjects With Overall Survival.
The time in months from the date of transplant to date of death from any cause or for surviving patients, to last follow-up. Patients who are alive and disease-free will be censored at last follow-up.
Measured: Day +100 and 1 year
Incidence of Infections
Number of subjects experiencing a grade ≥3 (CTCAE v5) viral, fungal and/or bacterial infections.
Measured: Day +28, Day +100 and 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2019
- Study start1 Mar 2020
- Primary completion1 Jun 2024
- Study completion17 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William R. Drobyski, MD, Medical College of Wisconsin
- Investigators
- William Drobyski, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04112810
- Sponsor's protocol ID
- PRO35737
- Status last verified
- Oct 2025
- First submitted
- 30 Sep 2019
- Last updated
- 21 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Runaas L, Fank S, Palen K, Szabo A, Rein LE, Ying G, Salzman N, Samanas L, Abedin S, Chhabra S, Hamadani M, Longo W, Shah NN, Haber J, Gradissimo A, Waters N, Peled JU, Johnson B, Kearl T, Drobyski WR. Tildrakizumab for the prophylaxis of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood Adv. 2026 Apr 28;10(8):2698-2710. doi: 10.1182/bloodadvances.2025019065.
PubMed 41632629
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Tildrakizumab for Prevention of Acute Graft-Versus-Host Disease
- ClinicalTrials.gov ID
- NCT04112810
- Acronym / sponsor ID
- PRO35737
- Conditions
- Hematologic Malignancies
- Keywords
- Graft-versus-host disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 1 Jun 2024 (actual)
- Study completion
- 17 Jun 2024 (actual)
- First posted
- 2 Oct 2019 (actual)
- Results
- Posted 4 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Rationale: GVHD remains a major cause of morbidity and mortality following myeloablative conditioning (MAC) alloHCT. Proinflammatory cytokines play a central role in initiation and development of acute GVHD and as such, inhibition of these cytokines has been examined for both prevention and treatment of GVHD. Interleukin (IL)-23 is a proinflammatory cytokine which the investigators' lab has shown to have a unique and selective role in induction of colonic inflammation during acute GVHD and that this cytokine serves as a critical mediator linking conditioning regimen-induced mucosal injury and endotoxin lipopolysaccharide (LPS) translocation to subsequent proinflammatory cytokine production and GVHD-associated pathological damage. Moreover, additional studies have demonstrated that blocking the IL-23 signaling pathway has not abrogated the graft-versus-tumor effect. Tildrakizumab is a commercially available anti-IL-23 antibody FDA approved for the treatment of moderate to severe psoriasis with good tolerance. The investigators hypothesize that blocking IL-23, with tildrakizumab, will reduce GVHD rates for patients undergoing MAC alloHCT without having an impact on relapse rates, thus improving GVHD-free relapse-free survival (GRFS).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tildrakizumab | Experimental | Drug: TildrakizumabTildrakizumab (IluymaTM) is a humanized monoclonal antibody that specifically binds to the IL-23p19 subunit of IL-23 to neutralize its function. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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).
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TildrakizumabAlso: Iluyma100 mg will be injected subcutaneously on Day -1, Day 28 ± 3, Day 112 ± 7, Day 196 ± 14, and Day 280 ± 14. | Drug | Tildrakizumab |
Primary outcome
GVHD-free Relapse-Free Survival
Time frame: 1 year
Number of subjects experiencing any of grade III-IV acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death at 12 months
13 secondary outcomes
Incidence of Chronic GVHD
Time frame: Day +180
Incidence of Chronic GVHD
Time frame: Day +365
Incidence of Acute GVHD
Time frame: Day +100 and Day +180
Incidence of Acute GI GVHD
Time frame: Day +100 and Day +180
Primary Graft Failure.
Time frame: Day 28
Secondary Graft Failure
Time frame: Up to Day 365
Hematopoietic Recovery According to Neutrophil Count Recovery
Time frame: Day +28
Hematopoietic Recovery According to Platelet Count Recovery
Time frame: Day +28
Non-relapsed Mortality.
Time frame: Day +100 and 1 year
Disease Relapse or Progression
Time frame: Day +100 and 1 year
The Number of Subjects With Progression-free Survival.
Time frame: Day +100 and 1 year
The Number of Subjects With Overall Survival.
Time frame: Day +100 and 1 year
Incidence of Infections
Time frame: Day +28, Day +100 and 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41632629Runaas L, Fank S, Palen K, Szabo A, Rein LE, Ying G, Salzman N, Samanas L, Abedin S, Chhabra S, Hamadani M, Longo W, Shah NN, Haber J, Gradissimo A, Waters N, Peled JU, Johnson B, Kearl T, Drobyski WR. Tildrakizumab for the prophylaxis of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood Adv. 2026 Apr 28;10(8):2698-2710. doi: 10.1182/bloodadvances.2025019065.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Drobyski, MD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tildrakizumab in people with Hematologic Malignancies, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GVHD-free Relapse-Free Survival (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04112810, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2025.