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)