Study of Pregnyl as Adjunct Therapy for High-Risk or Refractory Acute GVHD

Inclusion criteria

• Acute graft versus host disease (GVHD) fitting one of the following categories:

• High-Risk aGVHD (ARM 1): Pediatric or adult (ages 12-76 years) HCT recipients with high-risk acute GVHD, as determined by the refined MN acute GVHD risk score: http://z.umn.edu/MNAcuteGVHDRiskScore OR high risk on the basis of blood biomarkers (Ann Arbor Score 3 or amphiregulin ≥ 33 pg/ml) or
• Steroid-Refractory aGVHD (ARM 2): Pediatric or adult (ages 12-76 years) HCT recipient with grade II-IV steroid refractory or steroid-dependent acute GVHD, defined as any one of the following:

• No response of acute GVHD after at least 4 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
• Progression of acute GVHD within 3 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
• Failure to improve to at least grade II acute GVHD after 14 days of systemic corticosteroids, with initial doses of at least 2 mg/kg prednisone or equivalent
• Flare of acute GVHD of at least grade II/IV severity despite tapering dose of steroids being > 0.5 mg/kg/day.
• Adequate organ function at study enrollment defined as:

• Renal: 1.73m2Serum creatinine ≤2.5x upper limit of normal (ULN)
• Cardiac: Left ventricular ejection fraction (LVEF) ≥ 35%
• Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17 year olds)

Exclusion criteria

• Progressive malignancy
• Diagnosis of a hormone responsive malignancy
• Uncontrolled infection at initiation of protocol treatment
• Current thromboembolic disease requiring full-dose anticoagulation - patients receiving pharmacologic prophylaxis for thromboembolic disease will be eligible
• Active or recent (within prior 3 months) thrombus, irrespective of anticoagulation status
• Pregnancy as assessed on baseline blood hCG level
• Unwilling or unable to stop supplemental sex hormone therapy (estrogen, progesterone, and/or testosterone preparations)
• Women or men of childbearing potential unwilling to take adequate precautions to avoid pregnancy from the start of protocol treatment through 28 days after the last treatment

Screening Inclusion Criteria:

• Pediatric or adult (ages 0-76 years) HCT recipients
• Suspected high risk GVHD
• Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17 year olds)