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

NCT ID: NCT04128319

Last Updated: 2021-12-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-21
• Study Completion Date: 2020-02-17

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).

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.

Conditions

Steroid-Refractory Acute Graft Versus Host Disease

Keywords

Steroid-refractory acute GVHD; Acute GVHD; GVHD treatment

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

T-Guard Treatment

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

Group Type: EXPERIMENTAL

T-Guard

Intervention Type: 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).

Interventions

T-Guard

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).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patient must be at least 12.0 years of age at the time of consent.

2. 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.

3. 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.

4. 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.

5. 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.

Exclusion Criteria

1. Patients who have been diagnosed with overlap syndrome, that is, with any concurrent features of cGVHD.

2. Patients requiring any of the following: mechanical ventilation, vasopressor support, or hemodialysis.

3. Patients who have received any systemic treatment, besides steroids, as upfront treatment of aGVHD OR as treatment for SR-aGVHD.

4. Patients who have severe hypoalbuminemia, with an albumin of less than or equal to 1 g/dl.

5. Patients who have a CK level of greater than 5 times the upper limit of normal.

6. 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.

7. Patients with evidence of relapsed, progressing or persistent malignancy.

8. Patients with evidence of minimal residual disease requiring withdrawal of systemic immune suppression

9. Patients with known hypersensitivity to any of the components murine monoclonal antibodies (mAb) or Recombinant Ricin Toxin A-chain (RTA).

10. Patients who have received more than one allo-HSCT.

11. Patients with known human immunodeficiency virus infection.

12. 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.

13. 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.

14. 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.

15. 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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Blood and Marrow Transplant Clinical Trials Network

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Marrow Donor Program

OTHER

Sponsor Role: collaborator

Xenikos

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mehdi Hamadani, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

John Levine, MD

Role: STUDY_CHAIR

Icahn School of Medicine at Mount Sinai

Gabrielle Meyers, MD

Role: STUDY_CHAIR

Oregon Health and Science University

Locations

City of Hope National Medical Center

Duarte, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Children's National Medical Center

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

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

Indiana University

Indianapolis, Indiana, United States

University of Kansas

Westwood, Kansas, United States

University of Maryland

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University in St. Louis

St Louis, Missouri, United States

University of Nebraska

Omaha, Nebraska, United States

Mount Sinai Medical Center

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

University of Wisconsin

Madison, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 34815518 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2U10HL069294-11

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5U24HL138660

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BMTCTN1802

Identifier Type: -

Identifier Source: org_study_id