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Steroid-Refractory Acute Graft Versus Host DiseasePhase 32002NCT04934670

A Study to Compare T-Guard vs Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-vs-Host Disease (BMT CTN 2002)

A Phase 3 study testing T-Guard and Ruxolitinib in people with Steroid-Refractory Acute Graft Versus Host Disease, run by Xenikos at 48 sites in 9 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is an open-label, randomized, Phase 3, multicenter trial, which has been designed to compare the efficacy and safety of T-Guard to ruxolitinib in patients with Grade III or IV Steroid-Refractory acute Graft-Versus-Host Disease (SR-aGVHD). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
T-Guard and Ruxolitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
48 sitesin 9 countries
Study dates
16 Jun 2022to 19 Jan 2023
Phase
Phase 3
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

  • To be eligible to participate in this study, patients must meet the following:
  • Patients must be at least 18.0 years of age at the time of consent.
  • Patient has undergone first allo-HSCT from any donor source or graft source. Recipients of nonmyeloablative, reduced intensity, and myeloablative conditioning regimens are eligible.
  • Patients diagnosed with Grade III/IV SR-aGVHD after allo-HSCT. SR includes aGVHD initially treated at a lower steroid dose, but must meet one of the following criteria:
  • Progressed or new organ involvement after 3 days of treatment with methylprednisolone (or equivalent) of greater than or equal to 2 mg/kg/day
  • No improvement after 7 days of primary treatment with methylprednisolone (or equivalent) of greater than or equal to 2mg/kg/day
Show all 10Show fewer
  • Patients with visceral (GI and/or liver) plus skin aGVHD at methylprednisolone (or equivalent) initiation with improvement in skin GVHD without any improvement in visceral GVHD after 7 days of primary treatment with methylprednisolone (or equivalent) of greater than or equal to 2mg/kg/day
  • Patients who have skin GVHD alone and develop visceral aGVHD during treatment with methylprednisolone (or equivalent) of greater than or equal to 1mg/kg/day and do not improve after 3 days of greater than or equal to 2mg/kg/day Improvement or progression in organs is determined by comparing current organ staging to staging at initiation of methylprednisolone (or equivalent) treatment.
  • Patients must have evidence of myeloid engraftment (e.g., absolute neutrophil count greater than or equal to 0.5 × 109/L for 3 consecutive days if ablative therapy was previously used). Use of growth factor supplementation is allowed.
  • Patients or an impartial witness (in case the patient is capable of providing verbal consent but not capable of signing the informed consent form (ICF)) should have given written informed consent.

Who cannot join

  • Patients will be excluded from study entry if they meet any of the following exclusion criteria:
  • Patients who have a creatinine greater than or equal to 2mg/dL or estimated creatinine clearance less than 40 mL/min or those requiring hemodialysis.
  • Patients who have been diagnosed with active thrombotic microangiopathy (TMA), defined as meeting all the following criteria:
  • Greater than 4% schistocytes in blood (or equivalent if semiquantitative scale is used e.g., 3+ or 4+ schistocytes on peripheral blood smear)
  • De novo, prolonged or progressive thrombocytopenia (platelet count less than 50 x 109/L or 50% or greater reduction from previous counts)
  • Sudden and persistent increase in lactate dehydrogenase concentration greater than 2x the upper level of normal (ULN)
Show all 35Show fewer
  • Decrease in hemoglobin concentration or increased transfusion requirement attributed to Coombs-negative hemolysis
  • Decrease in serum haptoglobin
  • Patients who have previously received treatment with eculizumab.
  • Patients who have previously received checkpoint inhibitors (either before or after allo-HCT).
  • Patients who have been diagnosed with overlap syndrome, that is, with any concurrent features of cGVHD.
  • Patients requiring mechanical ventilation or vasopressor support.
  • Patients who have received any systemic treatment, besides steroids, as upfront treatment of aGVHD or as treatment for SR-aGVHD. Reinstitution of previously used GVHD prophylaxis agents (e.g., tacrolimus, cyclosporin, methotrexate [MTX], MMF) or substitutes in cases with previously documented intolerance will be permitted. Previous treatment with a janus kinase (JAK) inhibitor as part of GVHD prophylaxis or treatment is not allowed.
  • Patients who have severe hypoalbuminemia, with an albumin of less than or equal to 1 g/dl.
  • Patients who have a creatine kinase (CK) level of greater than 5 times the upper limit of normal.
  • Patients with uncontrolled infections. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. Progression of infection is defined as:
  • hemodynamic instability attributable to sepsis OR
  • new symptoms attributable to infection OR
  • worsening physical signs attributable to infection OR
  • worsening radiographic findings attributable to infection Patients with radiographic findings attributable to infection within 4 weeks prior to enrollment must have a repeat radiographic exam within one week of enrollment that documents absence of worsening.
  • Patients with evidence of relapsed, progressing, or persistent malignancy, or who have been treated for relapse after transplant, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse.
  • Patients with evidence of minimal residual disease requiring withdrawal of systemic immune suppression.
  • Patients with unresolved serious toxicity or complications (other than aGVHD) due to previous transplant.
  • History of sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD).
  • Patients with known hypersensitivity to any of the components murine monoclonal antibodies (mAb) or Recombinant Ricin Toxin A-chain (RTA).
  • Patients who have had treatment with any other investigational agent, device, or procedure within 21 days (or 5 half-lives, whichever is greater) prior to enrollment. An investigational agent is defined as medications without any known FDA or European Medicines Agency (EMA) approved indications.
  • Patients who have received more than one allo-HSCT.
  • Patients with known human immunodeficiency virus infection.
  • Patients who have a BMI greater than or equal to 35 kg/m2.
  • Patients who are taking sirolimus must discontinue prior to starting study treatment.
  • The sirolimus blood level must be less than 2 ng/mL prior to starting study treatment.
  • Female patients who are pregnant, breast feeding, or, if sexually active and of childbearing potential, unwilling to use effective birth control from start of treatment until 30 days after the last study treatment.
  • Male patients who are, if sexually active and with a female partner of childbearing potential, unwilling to use effective birth control from start of treatment until 65 days after the last study treatment.
  • Patients with any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the patient; or interfere with interpretation of study data.
  • Patients whose decision to participate might be unduly influenced by perceived expectation of gain or harm by participation, such as patients in detention due to official or legal order.

Trial locations and contacts

48 sites in 9 countries.

48 sites in 9 countries

United States12 sites

  • University of Alabama

    Birmingham, Alabama, 35294

  • Ohio State University

    Columbus, Ohio, 43210

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University of Wisconsin

    Madison, Wisconsin, 53705

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • University of Utah

    Salt Lake City, Utah, 84112

  • Washington University St. Louis

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33612

  • Wake Forest University

    Winston-Salem, North Carolina, 27109

Other trials in United States

France10 sites

  • Site FR341

    Angers

  • Site FR345

    Créteil

  • Site FR346

    La Tronche

  • Site FR355

    Lille

  • SiteFR354

    Nantes

  • SiteFR342

    Paris

  • SiteFR348

    Paris

  • Site FR356

    Pierre-Bénite

  • Site FR351

    Saint-Priest-en-Jarez

  • Site FR352

    Toulouse

Other trials in France

Germany7 sites

  • Site DE367

    Dresden

  • Site DE364

    Essen

  • Site DE371

    Hanover

  • Site DE368

    Heidelberg

  • Site DE360

    Leipzig

  • Site DE362

    Mainz

  • Site DE361

    Münster

Other trials in Germany

Spain7 sites

  • Site ES447

    Barcelona

  • Site ES446

    Madrid

  • Site ES442

    Salamanca

  • Site ES451

    Santander

  • Site ES452

    Seville

  • Site ES453

    Valencia

  • Site ES454

    Valencia

Other trials in Spain

Belgium6 sites

  • Site BE300

    Brussels

  • Site BE301

    Brussels

  • Site BE307

    Ghent

  • Site BE305

    Leuven

  • Site BE302

    Liège

  • Site BE303

    Yvoir

Other trials in Belgium

Netherlands3 sites

  • Site NL461

    Groningen

  • Site NL460

    Maastricht

  • Site NL463

    Nijmegen

Other trials in Netherlands

Croatia1 site

  • Site HR320

    Zagreb

Other trials in Croatia

Italy1 site

  • Site IT384

    Milan

Other trials in Italy

United Kingdom1 site

  • Site GB483

    Cardiff

Other trials in United Kingdom

About this study

Official title: A Phase 3, Randomized, Open-Label, Multicenter Study, to Compare T-Guard to Ruxolitinib for the Treatment of Patients With Grade III or IV Steroid-Refractory Acute Graft-Versus-Host Disease (SR-aGVHD)

This is an open-label, randomized, Phase 3, multicenter trial, which has been designed to compare the efficacy and safety of T-Guard to ruxolitinib in patients with Grade III or IV Steroid-Refractory acute Graft-Versus-Host Disease (SR-aGVHD). The primary hypothesis is that T-Guard treatment will improve the Day 28 complete response (CR) rate in patients with Grades III and IV SR-aGVHD compared to ruxolitinib.

Read the detailed description

Graft-vs-Host Disease (GVHD) is a complication that affects many hematopoietic stem cell transplant (HSCT) patients; it occurs when the new cells from a transplant attack the recipient's body. Acute GVHD (aGVHD) typically develops within the first three months after HSCT and is typically treated with steroid therapy. A significant fraction of the aGVHD population (10-50%) fail to respond to treatment and are deemed steroid-refractory (SR).

Participants that develop Grade III or IV SR aGVHD will be randomized to receive T-Guard or ruxolitinib and will be followed for approximately 180 days. Participants will be stratified by center region (US vs. Europe) and age group (at least 55 years vs. under 55). Participants randomized to the T-Guard arm will receive 4 doses administered intravenously as four 4-hour infusions, and participants randomized to the ruxolitinib arm will receive one dose administered orally twice a day. The primary analysis will include all participants that are randomized.

Being tested
T-Guard, Ruxolitinib
Keywords
T-Guard, Ruxolitinib, Steroid-Refractory, GVHD, Acute GVHD, aGVHD, Grade III, Grade IV, Complete Response (CR), Transplant, Hematopoietic Stem Cell Transplant (HSCT)
Medical subject headings
Lymphoma, Follicular, Pathologic Complete Response

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • T-GuardDrug

    T-Guard will be administered intravenously inpatient over 4 hours every 2 calendar days on Days 0, 2, 4, and 6, at a dose of 4mg/m2 Body Surface Area (BSA).

  • RuxolitinibDrug

    Also called Jakafi, Jakavi

    Ruxolitinib will be administered orally twice a day starting on Day 0 through Day 56, at a dose of 10mg. Ruxolitinib taper can be initiated starting on Day 56 for participants responding to treatment, tapering will be done according to institutional practices.

Study groups in NCT04934670
Study groupRoleWhat they receive
T-GuardExperimentalParticipants will be administered four doses of T-Guard intravenously for a 4-hour period every other day
Receives: Drug: T-Guard
RuxolitinibActive comparatorParticipants will take ruxolitinib twice daily for continuous daily dosing
Receives: Drug: Ruxolitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete Response (CR)

    The primary objective of this trial is to assess the rate of CR on Day 28 post-randomization in Grades III and IV SR-aGVHD patients treated with T-Guard treatment in comparison to ruxolitinib. Participants were classified as Day 28 CR if these three conditions were satisfied:

    1. Stage 0 aGVHD (no remaining symptoms) in the three target organs skin, bowel and liver, 2 . The participant is still alive at Day 28, 3 . No additional systemic treatment for aGVHD has been administered through Day 28.

    Measured: Day 28

Secondary outcomes (2)

  1. Overall Survival (OS)

    OS is defined as survival of death from any cause. The time from randomization until death from any cause will be described for each arm.

    Measured: Day 180

  2. Duration of Complete Response (DoCR)

    DoCR will be evaluated only in the set of participants who are in CR at Day 28 post-randomization. The primary definition of DoCR is the time from Day 28 until an aGVHD target organ worsens by at least 1 stage and requires a significant escalation in treatment, or death.

    Measured: Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jun 2021
  2. Study start16 Jun 2022
  3. Primary completion10 Nov 2022
  4. Study completion19 Jan 2023

Why it stopped: The study met the protocol defined stopping boundary for Day 60 mortality when comparing mortality between the T-Guard and ruxolitinib arms

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants will be randomized at a ratio of 1:1 between the treatment arms
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04934670
Sponsor's protocol ID
BMT CTN 2002
Other IDs
5U24HL138660-02, 2021-000343-53, XEN-TG-005, U10HL069294, U24HL138660
Acronym
2002
Status last verified
Apr 2022
First submitted
14 Jun 2021
Last updated
27 Aug 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Meyers G, Hamadani M, Martens M, Ali H, Chevallier P, Choe H, Harris AC, Holler E, van Hooren E, Klaassen W, Leifer E, van Oosterhout Y, Perez L, Pusic I, Stelljes M, van der Velden W, Ammatuna E, Beauvais D, Cornillon J, Maziarz RT, Schetelig J, Romeril J, MacMillan ML, Levine JE, Socie G. Anti-CD3/CD7 immunoconjugate (T-Guard) for severe, steroid-refractory GVHD: final report of BMT CTN 2002. Bone Marrow Transplant. 2023 Dec;58(12):1416-1418. doi: 10.1038/s41409-023-02110-4. Epub 2023 Sep 25. No abstract available.

    PubMed 37749187

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing T-Guard and Ruxolitinib in people with Steroid-Refractory Acute Graft Versus Host Disease, run by Xenikos at 48 sites in 9 countries.

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 10 inclusion and 35 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: stopped early, as of the sponsor's last update on 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States, France, Germany, Spain, Belgium and 4 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 27 Aug 2024). 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?

Complete Response (CR) (time frame: Day 28). 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 NCT04934670, 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 27 Aug 2024.

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