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

Graft vs Host Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02525029
• Other study ID #: 2014LS020
• Secondary ID: NCI-2015-02022
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2016
• Est. completion date: April 2022

Study information

• Verified date: December 2023
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: April 2022
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 76 Years

Eligibility

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)

Related Conditions & MeSH terms

• Graft vs Host Disease

Intervention

Drug:
• Pregnyl®
Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.

Locations

Country	Name	City	State
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: MTD (USP hCG)	Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD). Dosage measured as (USP hCG/pg EGF/mm^2).	Day 14 after initiation of protocol therapy
Primary	Phase I: MTD (pg EGF/m^2)	Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD). Dosage measured as (USP hCG/pg EGF/m^2).	Day 14 after initiation of protocol therapy
Primary	Number of Patients With Complete Response	Percentage of complete response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Complete response is defined as a Stage of 0 for all organs with no additional intervening therapy for their GVHD.	Day 28 after initiation of protocol therapy
Primary	Number of Patients With Partial Response	Percentage of partial response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Partial response is defined as improvement by at least 1 stage in all involved organs without progression in others with no additional intervening therapy for their GVHD.	Day 28 after initiation of protocol therapy
Primary	Number of Patients With Mixed Response	Percentage of mixed response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Mixed Response is defined as improvement in one organ with deterioration in another organ manifesting symptoms of GVHD or development of symptoms of GVHD in a new organ.	Day 28 after initiation of protocol therapy
Primary	Number of Patients With No Response	Percentage of no response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. No response is defined as deterioration of any organ involved.	Day 28 after initiation of protocol therapy
Secondary	Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl®	Safety and feasibility of hCG supplementation with Pregnyl® in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory aGVHD.	Day 70 after initiation of protocol therapy
Secondary	Number of Participants With Incidence of aGVHD Flare	Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at day 28.	Day 28 after initiation of protocol therapy
Secondary	Number of Participants With Incidence of aGVHD Flare	Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at day 56.	Day 56 after initiation of protocol therapy
Secondary	Rate of Participants Who Fail Treatment at Day 28	Rate of treatment failure for acute GVHD at day 28 after initiation of protocol therapy to historical controls.	Day 28 after initiation of protocol therapy
Secondary	Rate of Participants Who Fail Treatment at Day 56	Rate of treatment failure for acute GVHD at day 56 after initiation of protocol therapy to historical controls.	Day 56 after initiation of protocol therapy