Graft vs Host DiseasePhase 1/2NCT02525029

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

A Phase 1/2 study testing Pregnyl® in people with Graft vs Host Disease, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages Up to 76 years
Conditions the study is for: Graft vs Host Disease
What is being tested?: Pregnyl®
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 53 participants
Where: 1 siteUnited States
Study dates: Mar 2016to Apr 2022
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 76 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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

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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)

Who cannot join

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

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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)

Trial locations and contacts

1 site in 1 country.

United States1 site

Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455

Other trials in United States

About this study

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

Conditions: Graft vs Host Disease
Being tested: Pregnyl®
Keywords: GVHD
Medical subject headings: Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Pregnyl®Drug
Also called Human chorionic gonadotropin (hCG)
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.

Study groups in NCT02525029
Study group	Role	What they receive
Arm 1: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 1: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2A: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2A: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2A: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2B: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2B: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2	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. Receives: Drug: Pregnyl®
Arm 1: Phase 2 MTD	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 Receives: Drug: Pregnyl®
Arm 2A: MTD	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 Receives: Drug: Pregnyl®
Arm 2B: MTD	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 Receives: Drug: Pregnyl®

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: Day 14 after initiation of protocol therapy
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).
Measured: Day 14 after initiation of protocol therapy
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.
Measured: Day 28 after initiation of protocol therapy
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.
Measured: Day 28 after initiation of protocol therapy
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.
Measured: Day 28 after initiation of protocol therapy
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.
Measured: Day 28 after initiation of protocol therapy

Secondary outcomes (5)

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.
Measured: Day 70 after initiation of protocol therapy
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.
Measured: Day 28 after initiation of protocol therapy
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.
Measured: Day 56 after initiation of protocol therapy
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.
Measured: Day 28 after initiation of protocol therapy
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.
Measured: Day 56 after initiation of protocol therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2016Apr 2022

First posted17 Aug 2015 (estimated)
Study startMar 2016
Primary completionMay 2021
Study completionApr 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Graft vs Host DiseaseStudies of the same condition, open and under way.
More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Supportive care
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 53 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02525029
Sponsor's protocol ID: 2014LS020
Other IDs: NCI-2015-02022
Status last verified: Dec 2023
First submitted: 14 Jul 2015
Last updated: 14 Dec 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Holtan SG, Hoeschen A, Cao Q, Ustun C, Betts BC, Jurdi NE, Maakaron J, Rashidi A, Miller JS, Wagner JE, Blazar BR, Jacobson PA, Panoskaltsis-Mortari A, Weisdorf DJ, MacMillan ML. Phase II, Open-Label Clinical Trial of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor for Life-Threatening Acute Graft-versus-Host Disease. Transplant Cell Ther. 2023 Aug;29(8):509.e1-509.e8. doi: 10.1016/j.jtct.2023.05.021. Epub 2023 Jun 4.
PubMed 37279855
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.
PubMed 32236525

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Graft vs Host Disease

All Graft vs Host Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02525029
Acronym / sponsor ID: 2014LS020
Conditions: Graft vs Host Disease
Keywords: GVHD
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 53 participants (actual)
Lead sponsor: Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
Study start: Mar 2016 (actual)
Primary completion: May 2021 (actual)
Study completion: Apr 2022 (actual)
First posted: 17 Aug 2015 (estimated)
Results: Posted 14 Dec 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Supportive care
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 20

Arm	Type	Receives
Arm 1: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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	Experimental	Drug: Pregnyl®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

Who may qualify

Ages: Up to 76 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (11 listed)

Acute graft versus host disease (GVHD) fitting one of the following categories:
Adequate organ function at study enrollment defined as:
Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17 year olds)

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Pregnyl®Also: Human chorionic gonadotropin (hCG)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.	Drug	Arm 1: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2, Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2, Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2, Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2, Arm 1: Phase 2 MTD, Arm 1: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2, Arm 2A: MTD, Arm 2A: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2, Arm 2A: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2, Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2, Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2, Arm 2A: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2, Arm 2B: MTD, Arm 2B: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2, Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2, Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2, Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2, Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2, Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2, Arm 2B: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2

Primary outcome

Phase I: MTD (USP hCG)
Time frame: Day 14 after initiation of protocol therapy
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).
Phase I: MTD (pg EGF/m^2)
Time frame: Day 14 after initiation of protocol therapy
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).
Number of Patients With Complete Response
Time frame: Day 28 after initiation of protocol therapy
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.
Number of Patients With Partial Response
Time frame: Day 28 after initiation of protocol therapy
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.
Number of Patients With Mixed Response
Time frame: Day 28 after initiation of protocol therapy
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.
Number of Patients With No Response
Time frame: Day 28 after initiation of protocol therapy
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.

5 secondary outcomes

Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl®
Time frame: Day 70 after initiation of protocol therapy
Number of Participants With Incidence of aGVHD Flare
Time frame: Day 28 after initiation of protocol therapy
Number of Participants With Incidence of aGVHD Flare
Time frame: Day 56 after initiation of protocol therapy
Rate of Participants Who Fail Treatment at Day 28
Time frame: Day 28 after initiation of protocol therapy
Rate of Participants Who Fail Treatment at Day 56
Time frame: Day 56 after initiation of protocol therapy

Results and safety

Results posted to the registry on 14 Dec 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm 1: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2	0	0
Arm 1: Phase 2 Dose Level -2: 125 USP hCG/875 pg EGF/m^2	0	0
Arm 1: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2	0	0
Arm 1: Phase 2 Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2	0	0
Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2	2	2
Arm 1: Phase 2 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2	0	0
Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	2	2
Arm 1: Phase 2 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	0	0
Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2	9	9
Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2	13	13
Arm 2A: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2	0	0
Arm 2A: Phase 2 Dose Level -2: 125 USP hCG/875 pg EGF/m^2	0	0
Arm 2A: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2	0	0
Arm 2A: Phase 2 Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2	0	0
Arm 2A: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2	0	0
Arm 2A: Phase 2 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2	0	0
Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	1	1
Arm 2A: Phase 2 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	0	0
Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2	4	4
Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2	8	8
Arm 2B: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2	0	0
Arm 2B: Phase 2 Dose Level -2: 125 USP hCG/875 pg EGF/m^2	0	0
Arm 2B: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2	0	0
Arm 2B: Phase 2 Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2	0	0
Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2	2	1
Arm 2B: Phase 2 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2	0	0
Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	1	1
Arm 2B: Phase 2 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	0	0
Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2	5	5
Arm 2B: Phase 2 Dose Level 3 2,000 USP	1	1
Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2	2	2
Arm 2B: Phase 2 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2	0	0
Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m	3	3
Arm 2B: Phase 2 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m	0	0

Primary outcome: Phase I: MTD (USP hCG)

Time frame: Day 14 after initiation of protocol therapy. Number. Unit: Pregnyl dosage (USP hCG)

Measure	1: High-Risk aGVHD n = 26	2a: Steroid-Dependent aGVHD n = 13	2b: Steroid-Refractory aGVHD n = 12
Value	2000	2000	5000

Primary outcome: Phase I: MTD (pg EGF/m^2)

Time frame: Day 14 after initiation of protocol therapy. Number. Unit: Pregnyl dosage (pg EGF/m^2)

Measure	1: High-Risk aGVHD n = 26	2a: Steroid-Dependent aGVHD n = 13	2b: Steroid-Refractory aGVHD n = 12
Value	14000	14000	34000

Primary outcome: Number of Patients With Complete Response

Time frame: Day 28 after initiation of protocol therapy. Number. Unit: participants

Measure	Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n = 2	Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n = 2	Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 9	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 13	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n = 1	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 4	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 8	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n = 2	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n = 1	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 5	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 1	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 n = 2	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 n = 3
Value	2	2	4	7	1	3	5	1	0	2	0	0	1

Primary outcome: Number of Patients With Partial Response

Time frame: Day 28 after initiation of protocol therapy. Number. Unit: participants

Measure	Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n = 2	Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n = 2	Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 9	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 13	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n = 1	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 4	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 8	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n = 2	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n = 1	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 5	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n = 1	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 n = 2	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 n = 3
Value	0	0	0	1	0	0	1	0	1	1	0	0	1

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 70 Days after first treatment. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2	1 of 2 (50%)	1 of 2 (50%)	0 of 2
Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	1 of 2 (50%)	1 of 2 (50%)	1 of 2
Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2	1 of 9 (11.1%)	3 of 9 (33.3%)	0 of 9
Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2	2 of 13 (15.4%)	6 of 13 (46.2%)	0 of 13
Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	1 of 1 (100%)	1 of 1 (100%)	0 of 1
Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2	2 of 4 (50%)	2 of 4 (50%)	1 of 4
Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2	4 of 8 (50%)	5 of 8 (62.5%)	0 of 8
Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2	2 of 2 (100%)	2 of 2 (100%)	0 of 2
Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2	1 of 1 (100%)	1 of 1 (100%)	1 of 1
Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2	5 of 5 (100%)	3 of 5 (60%)	0 of 5
Arm 2B: Phase 2 Dose Level 3 2,000 USP	0 of 1 (0%)	1 of 1 (100%)	1 of 1
Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2	2 of 2 (100%)	2 of 2 (100%)	1 of 2
Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m	3 of 3 (100%)	1 of 3 (33.3%)	1 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37279855Holtan SG, Hoeschen A, Cao Q, Ustun C, Betts BC, Jurdi NE, Maakaron J, Rashidi A, Miller JS, Wagner JE, Blazar BR, Jacobson PA, Panoskaltsis-Mortari A, Weisdorf DJ, MacMillan ML. Phase II, Open-Label Clinical Trial of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor for Life-Threatening Acute Graft-versus-Host Disease. Transplant Cell Ther. 2023 Aug;29(8):509.e1-509.e8. doi: 10.1016/j.jtct.2023.05.021. Epub 2023 Jun 4.
Derived from this study: PubMed 32236525Holtan 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Shernan Holtan, MD principal investigator

University of Minnesota

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pregnyl® in people with Graft vs Host Disease, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: MTD (USP hCG) (time frame: Day 14 after initiation of protocol therapy). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02525029, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2023.