Please assess the completion status of the following clinical trial:

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

Study Design Characteristics:
- Allocation: NON_RANDOMIZED
- Intervention Model: SEQUENTIAL
- Observational Model: None
- Primary Purpose: SUPPORTIVE_CARE
- Time Perspective: None
- Masking: NONE
- Phase: PHASE1/PHASE2
- Number of Arms: 20.0

Eligibility Criteria:
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)

- Gender: ALL
- Minimum Age: None
- Maximum Age: 76 Years
- Healthy Volunteers: f

Study Arms:
- Arm 1: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 1: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2A: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2A: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2A: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2B: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2B: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 (Type: EXPERIMENTAL): Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.~The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT).~Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
- Arm 1: Phase 2 MTD (Type: EXPERIMENTAL): After completion of the dose finding trial for each arm, the final doses will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of the activity level for Arm 1 and Arm 2. If the phase I trial enrolls fewer than 13 patients at the MTD, we will employ Simon's Minmax two-stage design with the possibility to discontinue after the 1st stage if the response rate is low
- Arm 2A: MTD (Type: EXPERIMENTAL): After completion of the dose finding trial for each arm, the final doses will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of the activity level for Arm 1 and Arm 2. If the phase I trial enrolls fewer than 13 patients at the MTD, we will employ Simon's Minmax two-stage design with the possibility to discontinue after the 1st stage if the response rate is low
- Arm 2B: MTD (Type: EXPERIMENTAL): After completion of the dose finding trial for each arm, the final doses will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of the activity level for Arm 1 and Arm 2. If the phase I trial enrolls fewer than 13 patients at the MTD, we will employ Simon's Minmax two-stage design with the possibility to discontinue after the 1st stage if the response rate is low

Based on this trial design, predict the completion outcome and termination type (if applicable).