Ruxolitinib, Human Chorionic Gonadotropin (uhCG/EGF), and Dose De-escalated Corticosteroids

Acute-graft-versus-host Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05123040
• Other study ID #: 2020LS098
• Secondary ID: MT2020-28
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 5, 2023
• Est. completion date: September 2028

Study information

• Verified date: June 2024
• Source: Masonic Cancer Center, University of Minnesota
• Contact: Cancer Center Clinical Trials Office
• Phone: 612 624 2620
• Email: ccinfo[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: September 2028
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute-graft-versus-host Disease
• Graft vs Host Disease

Intervention

Drug:
• Ruxolitinib 10 MG Oral Tablet
By mouth twice daily through day 56, then tapered
• hCG
2,000 units/m2 SQ every other day x 3 doses, followed by twice weekly x 14 doses
• Corticosteroids
Dose level 1 (starting dose) = 1 mg/kg Dose level 2 = 0.5 mg/kg Dose level 3 = 0.25 mg/kg Dose level 4 = 0.1 mg/kg Dose level 5 = 0 mg/kg • If dose level 1 is determined to be below the Recommended Phase 2 Dose (RP2D), the dose will be escalated: Dose level -1 = 1.5 mg/kg Dose level -2 = 2 mg/kg

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	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	Plan report patients proportions and their 95% confidence intervals of paitents who experience dose limiting toxicity. Determine best dose based on DLT criteria by CTCAE v5.0; Thrombosis requiring anticoagulation; Ascites (grade 3-5); Ovarian hyperstimulation syndrome	28 days after therapy
Primary	Best response of treatment in adult and children	proportions of complete, partial, mixed, and no response among surviving patients at days 28 after initiation of protocol therapy in pediatric and adult patients with Minnesota high-risk aGVHD	28 days after therapy
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Report any type of adverse event caused by a drug cause by dose of steroids in combination of ruxolitinib and uhCG/EGF.; Due to the complex medical condition of the GVHD patient, monitoring for adverse events will focus on the following events beginning with the date consent is signed and continuing for 30 days after the subject has completed or discontinued from the study or has taken last dose of the study drug.; Rehospitalization; Death; Hematologic (grade 3-5 cytopenia); Infections (grade 3-5); Hyperglycemia (grade 3-5); Steroid myopathy (grade 3-5)	30 days after treatment
Secondary	Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment	Find proportion of incidence of acute GVHD	28 days after treatment
Secondary	Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment	Find proportion of incidence of acute GVHD	56 days after treatment
Secondary	Compare the rate of treatment failure for acute GVHD after initiation of protocol therapy to historical controls	Compare count of treatment failure to other number of failures in other historical protocols	28 days after treatment
Secondary	Compare the rate of treatment failure for acute GVHD after initiation of protocol therapy to historical controls	Compare count of treatment failure to other number of failures in other historical protocols	56 days after treatment
Secondary	To assess patient quality of life on study	Have participants take an overall survival survey	6 month after treatment
Secondary	Determine 1-year overall survival	Provide proportions and their 95% confidence intervals of patients still alive at one year post-treatment	1 year post treatment
Secondary	Non-relapse mortality (death without recurrent or progressive disease after allo-HSCT)	Provide proportions and their 95% confidence intervals of patients who expedience a non-relapse mortality.	1 year post treatment
Secondary	Collect blood samples and rectosigmoid biopsies for future correlative studies	Give a count of the number of patients who had blood and rectosigmoid biopsies	1 year after treament