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

NCT04934670 | Terminated Phase 3 Results DMC FDA Drug

• 6 other identifiers: BMT CTN 20025U24HL138660-022021-000343-53XEN-TG-005U10HL069294U24HL138660
• Study Type: interventional
• Target: 12
• Locations: 9 countries
• Sites: 48

Brief 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). 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.

Conditions

Steroid-Refractory Acute Graft Versus Host Disease

Keywords

T-Guard; Ruxolitinib; Steroid-Refractory; GVHD; Acute GVHD; aGVHD; Grade III; Grade IV; Complete Response (CR); Transplant; Hematopoietic Stem Cell Transplant (HSCT)

Outcome Measures

Primary Outcomes (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.

  Day 28

Secondary Outcomes (2)

• Overall Survival (OS)

  Day 180

• Duration of Complete Response (DoCR)

  Day 28

Study Arms (2)

T-Guard

EXPERIMENTAL

Participants will be administered four doses of T-Guard intravenously for a 4-hour period every other day

Drug: T-Guard

Ruxolitinib

ACTIVE COMPARATOR

Participants will take ruxolitinib twice daily for continuous daily dosing

Drug: Ruxolitinib

Interventions

T-Guard DRUG

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).

T-Guard

Ruxolitinib DRUG

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.

Also known as: Jakafi, Jakavi

Ruxolitinib

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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)
• 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:

Sponsors & Collaborators

• Xenikos: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Blood and Marrow Transplant Clinical Trials Network: collaborator
• National Cancer Institute (NCI): collaborator
• National Marrow Donor Program: collaborator

Study Sites (48)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Washington University St. Louis

St Louis, Missouri, 63110, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27109, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Site BE300

Brussels, Belgium

Location

Site BE301

Brussels, Belgium

Location

Site BE307

Ghent, Belgium

Location

Site BE305

Leuven, Belgium

Location

Site BE302

Liège, Belgium

Location

Site BE303

Yvoir, Belgium

Location

Site HR320

Zagreb, Croatia

Location

Site FR341

Angers, France

Location

Site FR345

Créteil, France

Location

Site FR346

La Tronche, France

Location

Site FR355

Lille, France

Location

SiteFR354

Nantes, France

Location

SiteFR342

Paris, France

Location

SiteFR348

Paris, France

Location

Site FR356

Pierre-Bénite, France

Location

Site FR351

Saint-Priest-en-Jarez, France

Location

Site FR352

Toulouse, France

Location

Site DE367

Dresden, Germany

Location

Site DE364

Essen, Germany

Location

Site DE371

Hanover, Germany

Location

Site DE368

Heidelberg, Germany

Location

Site DE360

Leipzig, Germany

Location

Site DE362

Mainz, Germany

Location

Site DE361

Münster, Germany

Location

Site IT384

Milan, Italy

Location

Site NL461

Groningen, Netherlands

Location

Site NL460

Maastricht, Netherlands

Location

Site NL463

Nijmegen, Netherlands

Location

Site ES447

Barcelona, Spain

Location

Site ES446

Madrid, Spain

Location

Site ES442

Salamanca, Spain

Location

Site ES451

Santander, Spain

Location

Site ES452

Seville, Spain

Location

Site ES453

Valencia, Spain

Location

Site ES454

Valencia, Spain

Location

Site GB483

Cardiff, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37749187 RESULT

Related Links

• Blood and Marrow Transplant Clinical Trials Network Website

MeSH Terms

Conditions

Lymphoma, Follicular; Pathologic Complete Response

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed, which resulted in the preparation and submission to the FDA and European authorities of an abbreviated clinical study report that did not contain all the outcome measures as specified in the clinical protocol.

Results Point of Contact

• Title: Ypke van Oosterhout, custodian of Sponsor
• Organization: Xenikos BV (no longer in business)

ypke@me.com

+31 611 0177 611

Study Officials

• Mary Horowitz, MD, MS

  Center for International Blood and Marrow Transplant Research

  STUDY DIRECTOR

• Willem Klaasen

  Xenikos, BV

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized at a ratio of 1:1 between the treatment arms

Study Record Dates

• First Submitted: June 14, 2021
• First Posted: June 22, 2021
• Study Start: June 16, 2022
• Primary Completion: November 10, 2022
• Study Completion: January 19, 2023
• Last Updated: August 27, 2024
• Results First Posted: August 27, 2024

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10); GB (1); BE (6); IT (1); NL (3); ES (7); US (12); CR (1); DE (7)