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Steroid-Refractory Acute Graft Versus Host DiseasePhase 31802NCT04128319

T-Guard as Treatment for Steroid Refractory Acute GVHD (BMT CTN 1802)

A Phase 3 study testing T-Guard in people with Steroid-Refractory Acute Graft Versus Host Disease, run by Xenikos at 24 sites in United States.

Terminated

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

Official record
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Trial summary

The study is designed as an open-label, single arm Phase III, multicenter trial to evaluate the efficacy and safety of T-Guard treatment in patients with Steroid-Refractory acute Graft versus Host Disease (SR-aGVHD). Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
T-Guard
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
24 sitesUnited States
Study dates
21 Nov 2019to 17 Feb 2020
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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patient must be at least 12.0 years of age at the time of consent.
  • Patient has undergone first allo-HSCT from any donor source using bone marrow, peripheral blood stem cells, or cord blood. Recipients of nonmyeloablative, reduced intensity, and myeloablative conditioning regimens are eligible.
  • Patients diagnosed with SR-aGVHD after allo-HSCT. SR is defined as aGVHD that:
  • Progressed after 3 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day
  • No improvement after 7 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day.
  • Patients with visceral (GI and/or liver) plus skin aGVHD at prednisone (or equivalent) initiation with improvement in skin GVHD without any improvement in visceral GVHD after 7 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day
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  • Previously was treated with prednisone (or equivalent) of greater than or equal to 1mg/kg/day and aGVHD has developed in a previously uninvolved organ system
  • Progression and no improvement are defined in the protocol. Improvement or progression in organs is determined by comparing current organ staging to staging at initiation of prednisone (or equivalent) treatment. Staging is performed per MAGIC criteria.
  • Evidence of myeloid engraftment (e.g., absolute neutrophil count greater than or equal to 0.5 × 10^9/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. For patients less than 18 years of age, a written informed consent of the parents or guardian and written assent of the patient will be obtained, per the local requirements.

Who cannot join

  • Patients who have been diagnosed with overlap syndrome, that is, with any concurrent features of cGVHD.
  • Patients requiring any of the following: mechanical ventilation, vasopressor support, or hemodialysis.
  • Patients who have received any systemic treatment, besides steroids, as upfront treatment of aGVHD OR as treatment for SR-aGVHD.
  • Patients who have severe hypoalbuminemia, with an albumin of less than or equal to 1 g/dl.
  • Patients who have a 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. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
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  • Patients with evidence of relapsed, progressing or persistent malignancy.
  • Patients with evidence of minimal residual disease requiring withdrawal of systemic immune suppression
  • Patients with known hypersensitivity to any of the components murine monoclonal antibodies (mAb) or Recombinant Ricin Toxin A-chain (RTA).
  • Patients who have received more than one allo-HSCT.
  • Patients with known human immunodeficiency virus infection.
  • 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 infusion of T-Guard.
  • 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 infusion of T-Guard.
  • 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

24 sites in 1 country.

24 sites in 1 country

United States24 sites
  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University

    Atlanta, Georgia, 30322

  • University of Maryland

    Baltimore, Maryland, 21201

  • Johns Hopkins University

    Baltimore, Maryland, 21231

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Ohio State University

    Columbus, Ohio, 43210

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Minnesota

    Minneapolis, Minnesota, 55414

  • Mount Sinai Medical Center

    New York, New York, 10029

  • University of Nebraska

    Omaha, Nebraska, 68198

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Utah

    Salt Lake City, Utah, 84112

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Washington University in St. Louis

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33612

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • University of Kansas

    Westwood, Kansas, 66205

Other trials in United States

About this study

Official title: An Open-Label, Single-Arm, Multicenter Study, of Combination Anti-CD3/CD7 Immunotoxin (T-Guard) for Steroid-Refractory Acute Graft-versus-Host Disease)

The study is designed as an open-label, single arm Phase III, multicenter trial to evaluate the efficacy and safety of T-Guard treatment in patients with Steroid-Refractory acute Graft versus Host Disease (SR-aGVHD).

Read the detailed description

Allogeneic Hematopoietic Cell Transplantation (allo-HSCT) is a potent immunotherapy with curative potential for several hematological disorders. Improvements in survival following allo-HSCT have led to its increasing use, but the leading cause of non-relapse mortality (NRM) remains graft-versus-host-disease (GVHD. Despite recent advances in the understanding of transplantation immune tolerance, aGVHD is a frequent and major complication of allo-HSCT involving activation of donor T-lymphocytes, which ultimately causes host tissue damage. T-Guard has a rapid onset, preferential killing of activated T cells, and short half-life, leading to depletion of allo-reactive T cells and quick post-treatment reconstitution of the immune system.

Being tested
T-Guard
Keywords
Steroid-refractory acute GVHD, Acute GVHD, GVHD treatment

What participants receive

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

  • T-GuardDrug

    Patients will receive 4 doses of T-Guard treatment, administered intravenously as four 4-hour infusions at least two calendar days (no less than 40 hours) apart. Each dose consists of 4 mg/m^2 Body Surface Area (BSA).

Study groups in NCT04128319
Study groupRoleWhat they receive
T-Guard TreatmentExperimentalPatients will receive T-Guard for treatment of steroid-refractory acute GVHD.
Receives: Drug: T-Guard

What is being measured

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

  1. Complete Response (CR)

    Complete Response at Day 28 is defined as a score of 0 for the GVHD staging in all evaluable organs at the Day 28 visit along with freedom from additional systemic therapy for treatment of acute GVHD.

    Measured: Day 28

Secondary outcomes (17)
  1. Duration of Complete Response (DoCR)

    Evaluate the duration of complete response (DoCR) Early Trial Closure.

    Measured: Through Day 180

  2. Overall Survival (OS)

    Estimate the overall survival (OS) at Day 30.

    Measured: Day 30

  3. Overall Response Rate (CR or Partial Response (PR))

    Estimate the overall response rate (CR or partial response (PR)) at Days 14, 28, and 56.

    Measured: Days 14, 28, and 56

  4. Proportions of CR, PR, Mixed Response (MR), no Response (NR) and Progression

    Describe proportions of CR, PR, mixed response (MR), no response (NR), and progression of aGVHD at Days 7, 14, 28, and 56.

    Measured: Days 7, 14, 28, and 56

  5. Non-Relapse Mortality (NRM)

    Estimate the cumulative incidence of non-relapse mortality (NRM) at Days 100 and 180.

    Measured: Days 100 and 180

  6. Relapse-free Survival

    Estimate relapse-free survival at Day 180.

    Measured: Days 180

  7. GVHD-free Survival

    Estimate GVHD-free survival at Days 90 and 180

    Measured: Days 90 and 180

  8. Cumulative Incidence of Chronic GVHD

    Estimate the cumulative incidence of chronic GVHD (cGVHD) at Day 180

    Measured: Day 180

  9. Cumulative Incidence of Disease Relapse/Progression

    Estimate the cumulative incidence of disease relapse/progression at Day 180

    Measured: Day 180

  10. Incidence of Systemic Infections

    Describe the incidence of systemic infections

    Measured: initiation of T-Guard to 28 days post-last dose

  11. Incidence of Toxicities

    Describe the incidence of CTCAE v5 Grade 3-5 toxicities

    Measured: initiation of T-Guard to 28 days post-last dose

  12. Pharmacokinetics of T-Guard - Cinf

    Observed and model-predicted concentration of T-Guard at the end of infusion

    Measured: Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14)

  13. Pharmacokinetics of T-Guard - CL

    Systemic clearance of T-Guard

    Measured: Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14)

  14. Pharmacokinetics of T-Guard - AUC

    Model-predicted area under the curve from the start of the current infusion until the next infusion or until 48 hours following for the last infusion

    Measured: Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14)

  15. Pharmacokinetics of T-Guard - t1/2

    Model-predicted terminal half-life of T-Guard

    Measured: Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14)

  16. Pharmacokinetics of T-Guard - Vc

    Volume of the central compartment

    Measured: Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14)

  17. Immunogenicity

    Assess the immunogenicity of T-Guard via ADA responses in the form of human anti-SPV-T3a-RTA and anti-WT1-RTA -antibodies evaluated in serum samples

    Measured: Baseline, Days 7, 14, 28, 90, and 180

Timeline

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

  1. First posted16 Oct 2019
  2. Study start21 Nov 2019
  3. Primary completion17 Feb 2020
  4. Study completion17 Feb 2020

Why it stopped: Initiated a new randomized trial per discussion with FDA

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
Not applicable
Intervention model
Single group
Model description
A single group of patients will receive T-Guard for treatment of steroid-refractory acute GVHD.
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04128319
Sponsor's protocol ID
BMTCTN1802
Other IDs
2U10HL069294-11, 5U24HL138660
Acronym
1802
Status last verified
Dec 2021
First submitted
27 Sep 2019
Last updated
16 Dec 2021
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, Choe H, Dawson P, Harris AC, van Hooren E, Klaassen W, Leifer E, MacMillan ML, van Oosterhout Y, Perez L, Pusic I, Vo P, Levine JE. Lessons learned from early closure of a clinical trial for steroid-refractory acute GVHD. Bone Marrow Transplant. 2022 Feb;57(2):302-303. doi: 10.1038/s41409-021-01529-x. Epub 2021 Nov 23. No abstract available.

    PubMed 34815518

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing T-Guard in people with Steroid-Refractory Acute Graft Versus Host Disease, run by Xenikos at 24 sites 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 10 inclusion and 15 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 16 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites 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 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 4 Aug 2021). 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 NCT04128319, 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 16 Dec 2021.

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