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

NCT04128319 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: BMTCTN18022U10HL069294-115U24HL138660
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 24

Brief 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).

Conditions

Steroid-Refractory Acute Graft Versus Host Disease

Keywords

Steroid-refractory acute GVHD; Acute GVHD; GVHD treatment

Outcome Measures

Primary Outcomes (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.

  Day 28

Secondary Outcomes (17)

• Duration of Complete Response (DoCR)

  Through Day 180

• Overall Survival (OS)

  Day 30

• Overall Response Rate (CR or Partial Response (PR))

  Days 14, 28, and 56

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

  Days 7, 14, 28, and 56

• Non-Relapse Mortality (NRM)

  Days 100 and 180

Other Outcomes (9)

• Corticosteroid Dose

  Baseline, Days 28 and 56

• Rate of Near-CR

  Days 28 and 56

• Discontinuation of Systemic Steroids

  Day 180

Study Arms (1)

T-Guard Treatment

EXPERIMENTAL

Patients will receive T-Guard for treatment of steroid-refractory acute GVHD.

Drug: T-Guard

Interventions

T-Guard DRUG

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).

T-Guard Treatment

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

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 (24)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Kansas

Westwood, Kansas, 66205, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

University of Nebraska

Omaha, Nebraska, 68198, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 34815518 RESULT

Limitations and Caveats

Due to the early trial closure and limited study population, only a subset of the protocol-specified planned analyses were performed.

Results Point of Contact

• Title: Eric van Hooren, Chief Development Officer
• Organization: Xenikos

e.vanhooren@xenikos.com

+31 6 109 345 84

Study Officials

• Mehdi Hamadani, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• John Levine, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

• Gabrielle Meyers, MD

  Oregon Health and Science University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Model Details: A single group of patients will receive T-Guard for treatment of steroid-refractory acute GVHD.

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: October 16, 2019
• Study Start: November 21, 2019
• Primary Completion: February 17, 2020
• Study Completion: February 17, 2020
• Last Updated: December 16, 2021
• Results First Posted: August 4, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (24)