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

Primary Purpose

Acute-graft-versus-host Disease

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ruxolitinib 10 MG Oral Tablet
hCG
Corticosteroids
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute-graft-versus-host Disease focused on measuring aGVHD

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Masonic Cancer Center at University of MinnesotaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ruxolitinib;hCG (Pregnyl®) ;Corticosteroids

Arm Description

Ruxolitinib 10 mg by mouth twice daily (with dose adjustments as indicated) through day 56, followed by taper hCG (Pregnyl®) 2,000 units/m2 SQ every other day x 3 doses, followed by twice weekly x 14 doses (total 17 doses through day 56) Corticosteroids (Prednisone, or IV methylprednisolone equivalent) 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

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

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)
Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment
Find proportion of incidence of acute GVHD
Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment
Find proportion of incidence of acute GVHD
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
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
To assess patient quality of life on study
Have participants take an overall survival survey
Determine 1-year overall survival
Provide proportions and their 95% confidence intervals of patients still alive at one year post-treatment
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.
Collect blood samples and rectosigmoid biopsies for future correlative studies
Give a count of the number of patients who had blood and rectosigmoid biopsies

Full Information

First Posted
November 3, 2021
Last Updated
June 12, 2023
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT05123040
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 5, 2023 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute-graft-versus-host Disease
Keywords
aGVHD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ruxolitinib;hCG (Pregnyl®) ;Corticosteroids
Arm Type
Experimental
Arm Description
Ruxolitinib 10 mg by mouth twice daily (with dose adjustments as indicated) through day 56, followed by taper hCG (Pregnyl®) 2,000 units/m2 SQ every other day x 3 doses, followed by twice weekly x 14 doses (total 17 doses through day 56) Corticosteroids (Prednisone, or IV methylprednisolone equivalent) 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
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib 10 MG Oral Tablet
Intervention Description
By mouth twice daily through day 56, then tapered
Intervention Type
Drug
Intervention Name(s)
hCG
Other Intervention Name(s)
Pregnyl
Intervention Description
2,000 units/m2 SQ every other day x 3 doses, followed by twice weekly x 14 doses
Intervention Type
Drug
Intervention Name(s)
Corticosteroids
Other Intervention Name(s)
Prednisone, IV methylprednisolone
Intervention Description
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
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
28 days after therapy
Title
Best response of treatment in adult and children
Description
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
Time Frame
28 days after therapy
Secondary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Description
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)
Time Frame
30 days after treatment
Title
Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment
Description
Find proportion of incidence of acute GVHD
Time Frame
28 days after treatment
Title
Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment
Description
Find proportion of incidence of acute GVHD
Time Frame
56 days after treatment
Title
Compare the rate of treatment failure for acute GVHD after initiation of protocol therapy to historical controls
Description
Compare count of treatment failure to other number of failures in other historical protocols
Time Frame
28 days after treatment
Title
Compare the rate of treatment failure for acute GVHD after initiation of protocol therapy to historical controls
Description
Compare count of treatment failure to other number of failures in other historical protocols
Time Frame
56 days after treatment
Title
To assess patient quality of life on study
Description
Have participants take an overall survival survey
Time Frame
6 month after treatment
Title
Determine 1-year overall survival
Description
Provide proportions and their 95% confidence intervals of patients still alive at one year post-treatment
Time Frame
1 year post treatment
Title
Non-relapse mortality (death without recurrent or progressive disease after allo-HSCT)
Description
Provide proportions and their 95% confidence intervals of patients who expedience a non-relapse mortality.
Time Frame
1 year post treatment
Title
Collect blood samples and rectosigmoid biopsies for future correlative studies
Description
Give a count of the number of patients who had blood and rectosigmoid biopsies
Time Frame
1 year after treament

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cancer Center Clinical Trials Office
Phone
612 624 2620
Email
ccinfo@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sherman Holtan, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center at University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cancer Center Clinical Trials Office
Phone
612-624-2620
Email
ccinfo@umn.edu

12. IPD Sharing Statement

Learn more about this trial

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

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