Clinical trial NCT02525029: Study of Pregnyl as Adjunct Therapy for High-Risk or Refractory Acute GVHD
Official title: Phase I/II Study of Human Chorionic Gonadotropin and Epidermal Growth Factor Supplementation (Pregnyl®) to Support Tolerance and Repair As Adjunct Therapy in High-Risk or Refractory Acute Graft-Versus-Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Graft vs Host Disease
Keywords: GVHD
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2015-08-17
Enrollment: 53
Sex: ALL
Maximum age (years): 76
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to determine the maximum tolerated dose (MTD) of Pregnyl® when given in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk (Arm 1) or refractory/dependent (Arm 2) aGVHD.


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)

Primary outcomes:
measure: Phase I: MTD (USP hCG)
timeFrame: Day 14 after initiation of protocol therapy
measure: Phase I: MTD (pg EGF/m^2)
timeFrame: Day 14 after initiation of protocol therapy
measure: Number of Patients With Complete Response
timeFrame: Day 28 after initiation of protocol therapy
measure: Number of Patients With Partial Response
timeFrame: Day 28 after initiation of protocol therapy
measure: Number of Patients With Mixed Response
timeFrame: Day 28 after initiation of protocol therapy
measure: Number of Patients With No Response
timeFrame: Day 28 after initiation of protocol therapy
Secondary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl®
timeFrame: Day 70 after initiation of protocol therapy
measure: Number of Participants With Incidence of aGVHD Flare
timeFrame: Day 28 after initiation of protocol therapy
measure: Number of Participants With Incidence of aGVHD Flare
timeFrame: Day 56 after initiation of protocol therapy
measure: Rate of Participants Who Fail Treatment at Day 28
timeFrame: Day 28 after initiation of protocol therapy
measure: Rate of Participants Who Fail Treatment at Day 56
timeFrame: Day 56 after initiation of protocol therapy
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Shernan Holtan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Holtan SG, Hoeschen AL, Cao Q, Arora M, Bachanova V, Brunstein CG, Miller JS, Rashidi A, Slungaard A, Ustun C, Vercellotti GM, Warlick ED, Betts BC, El Jurdi N, He F, Chen C, Gandhi I, Wagner JE, Blazar BR, Jacobson PA, Shabaneh A, Wang J, Panoskaltsis-Mortari A, MacMillan ML, Weisdorf DJ. Facilitating resolution of life-threatening acute GVHD with human chorionic gonadotropin and epidermal growth factor. Blood Adv. 2020 Apr 14;4(7):1284-1295. doi: 10.1182/bloodadvances.2019001259.