Clinical trial NCT05123040: Ruxolitinib, Human Chorionic Gonadotropin (uhCG/EGF), and Dose De-escalated Corticosteroids
Official title: Ruxolitinib, Human Chorionic Gonadotropin (uhCG/EGF), and Dose De-escalated Corticosteroids for Treatment of Minnesota High-Risk Acute GVHD (aGVHD): A Phase I/II Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute-graft-versus-host Disease
Keywords: aGVHD
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2021-11-17
Enrollment: 55
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This multi-center center phase I/II study to establish the lowest possible recommended phase 2 dose (RP2D) of corticosteroids in conjunction with ruxolitinib and uhCG/EGF (a novel combination) for high-risk aGVHD.

This is a single arm study designed to determine the lowest dose of corticosteroids required (toxicity endpoint) without impairing GVHD complete response or partial response (CR/PR) at day 28 when given in conjunction with uhCG/EGF and ruxolitinib.

After completion of the corticosteroid dose finding, the final dose will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of efficacy of this novel drug combination for high-risk aGVHD.


Eligibility criteria: Inclusion Criteria:

HCT recipients over 12 years of age within the first 7 days of initial treatment of high-risk aGVHD, defined as:

* Newly diagnosed Minnesota high-risk aGVHD -OR-
* Newly diagnosed Minnesota standard risk aGVHD with plasma amphiregulin ≥ 33 pg/ml tested at the UMN Cytokine Reference Lab. For amphiregulin lab ordering information, see Fairview Lab Guide: http://labguide.fairview.org/showtest.asp?testid=6766\&format=long -OR-
* Newly diagnosed Minnesota standard risk aGVHD Ann Arbor 3 biomarkers tested by Viracor. For ordering information, see: https://www.viracor-eurofins.com/test-menu/403572p-agvhd-symptomatic- onset-algorithm/

  * Renal: Serum 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
* Uncontrolled bacterial, fungal, parasitic, or viral infection at initiation of protocol treatment
* Unwilling or unable to stop supplemental sex hormone therapy (estrogen, progesterone, and/or testosterone preparations)
* Unwilling or unable to stop GnRH antagonists, aromatase inhibitors, or anti-androgens
* History of a hormone responsive malignancy
* 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
* Women or men of childbearing potential unwilling to take adequate precautions to avoid unintended pregnancy from the start of protocol treatment through 30 days after the last treatment

Primary outcomes:
measure: Recommend the lowest possible dose for Phase II of corticosteroids when given in combination with ruxolitinib and uhCG/EGF in pediatric based on DLT frequency
timeFrame: 28 days after therapy
measure: Best response of treatment in adult and children
timeFrame: 28 days after therapy
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: 30 days after treatment
measure: Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment
timeFrame: 28 days after treatment
measure: Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment
timeFrame: 56 days after treatment
measure: Compare the rate of treatment failure for acute GVHD after initiation of protocol therapy to historical controls
timeFrame: 28 days after treatment
measure: Compare the rate of treatment failure for acute GVHD after initiation of protocol therapy to historical controls
timeFrame: 56 days after treatment
measure: To assess patient quality of life on study
timeFrame: 6 month after treatment
measure: Determine 1-year overall survival
timeFrame: 1 year post treatment
measure: Non-relapse mortality (death without recurrent or progressive disease after allo-HSCT)
timeFrame: 1 year post treatment
measure: Collect blood samples and rectosigmoid biopsies for future correlative studies
timeFrame: 1 year after treament
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Sherman Holtan, MD
role: PRINCIPAL_INVESTIGATOR
References: