T-Guard as Treatment for Steroid Refractory Acute GVHD (BMT CTN 1802)
Condition: Steroid-Refractory Acute Graft Versus Host Disease
MeSH terms: Graft vs Host Disease
Intervention: T-Guard
Intervention description: 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).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: A single group of patients will receive T-Guard for treatment of steroid-refractory acute GVHD.
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Steroid-refractory acute GVHD; Acute GVHD; GVHD treatment

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).
    

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.