Study of US-ATG-F to Prevent Chronic Graft Versus Host Disease (GVHD)

• Acute GVHD [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Incidence of and time to
• Chronic GVHD [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Incidence of and time to mild to severe, moderate to severe, and severe
• Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Transplant related mortality
• Relapse [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Incidence of and time of
• Systemic immunosuppressive medication for treatment of chronic GVHD [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Incidence of and time to start of

• Incidence of and time to acute GVHD [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Incidence of and time to mild to severe, moderate to severe, and severe chronic GVHD [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Incidence of and time of relapse [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
• Incidence of and time to start of systemic immunosuppressive medication for treatment of chronic GVHD [ Time Frame: 12 months ] [ Designated as safety issue: No ]

The study objective is to compare the efficacy and safety of US-ATG-F as a supplement to standard of care prophylaxis versus standard of care prophylaxis alone in moderate to severe chronic GVHD-free survival.

This study is randomized, prospective, double-blind, placebo-controlled, phase 3 study evaluating the prevention of moderate to severe chronic GVHD in patients undergoing bone marrow or peripheral blood stem cell transplantation from matched, unrelated donors for acute leukemia and myelodysplastic syndrome during the first year after transplant.

Patients meeting all the inclusion and none of the exclusion criteria will be randomized (1:1). All patients will receive premedication and study drug 3 days prior to transplantation.

• GVHD
• Adult Acute Myeloid Leukemia
• Adult Acute Lymphoid Leukemia
• Myelodysplastic Syndrome

• Biological: US-ATG-F
  20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-12 hours 3 days prior to transplantation
  Other Name: Anti-human-T-lymphocyte Immune Globulin, Rabbit
• Biological: Placebo
  250 mL normal saline, IV infusion over 6-12 hours 3 days prior to transplantation

• Active Comparator: US-ATG-F
  20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-12 hours 3 days prior to transplantation
  Intervention: Biological: US-ATG-F
• Placebo Comparator: Placebo
  250 mL normal saline, IV infusion over 6-12 hours 3 days prior to transplantation
  Intervention: Biological: Placebo

Key Inclusion Criteria:

• Patients designated to undergo allogeneic peripheral blood or bone marrow stem cell transplantation following the diagnosis of one of the primary diseases in early or intermediate disease status (i.e., acute myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndrome)
• Patients with an unrelated HLA-A,-B, -C and -DRBI matched donor
• Patients with a Karnofsky Performance Score ≥ 70%

Key Exclusion Criteria:

• Clinically significant concomitant diseases (i.e., cardiac, pulmonary, renal and CNS)
• Bacterial, viral, or fungal infections
• Known positive for Hepatitis B surfaces antigen, or Hepatitis C antibody, or who have been tested positive for HIV
• Patients with any concurrent malignancy. Cancer treated with curative intent < 5 years previously will not be allowed except for patients with resected basal cell carcinoma or treated cervical carcinoma in situ
• Known contraindications to the administration of rabbit immunoglobulin antibodies
• Hypersensitivity to methylprednisolone, tacrolimus, methotrexate or any excipients contains in these products