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Belumosudil for the Pre-emptive Treatment of Patients With Chronic Graft Versus Host Disease

Primary Purpose

Chronic Graft Versus Host Disease

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Belumosudil
Biospecimen Collection
Electronic Health Record Review
Placebo Administration
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Graft Versus Host Disease

Eligibility Criteria

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

Inclusion Criteria: At least one diagnostic or distinctive cGVHD manifestation(s), but patients do not need to meet National Institute of Health (NIH) criteria for cGVHD If eye involvement only, cGVHD must be confirmed on exam by an ophthalmologist or optometrist No new immune suppressive therapy added within preceding 2 weeks prior to study enrollment for any indication Continuation of agents previously given as either GVHD prophylaxis or acute/late acute GVHD therapy are permitted. Modification of dose of these agents for targeting of therapeutic drug levels is permitted, as are decreases in existing prednisone dose based on routine clinical tapering practices. Increases in prednisone are not allowed in the 2 weeks prior to enrollment Age 18 and older Karnofsky performance score >= 70 Able to take oral medications Signed informed consent Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) Total bilirubin =< 1.5 x ULN Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 Female subjects of childbearing potential have a negative serum or urine pregnancy test at screening. Females of childbearing potential are defined as sexually mature females without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, females who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression Sexually active females of childbearing potential enrolled in the study must agree to use two forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control includes: Intrauterine device (IUD) plus one barrier method Stable doses of hormonal contraception for at least 3 months (eg, oral, injectable, implant, transdermal) plus one barrier method 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gel that contain a chemical to kill sperm); or A vasectomized partner For male subjects who are sexually active and who are partners of females of childbearing potential: Agreement to use two forms of contraception as per above and to not donate sperm during the treatment period and for at least 3 months after the last dose of study drug No evidence of active malignancy Exclusion Criteria: Any systemic immune suppressive treatment for cGVHD (topical or local therapies are allowed) Plan to start systemic immune suppressive therapy for cGVHD or increase steroid dose within 14 days after planned start of study medication 0.25 mg/kg/day or higher prednisone dose at time of screening History of non-compliance that in the investigator's opinion would interfere with study participation Uncontrolled psychiatric illness Female subject who is pregnant or breast feeding Previous therapy with belumosudil Known allergy/sensitivity to belumosudil or any other ROCK2 inhibitor Treatment with another investigational agent within 28 days (or 5 half-lives, whichever is greater) of enrollment

Sites / Locations

  • Moffitt Cancer Center
  • Mass General Cancer Center
  • Dana Farber Cancer Institute
  • Memorial Sloan Kettering Cancer Center
  • Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (Belumosudil)

Arm II (Placebo)

Arm Description

Patients receive belumosudil PO QD or BID if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study.

Patients receive a placebo PO QD or BID if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study.

Outcomes

Primary Outcome Measures

Time to start of subsequent systemic immune suppressive treatment for chronic graft versus host disease (cGVHD)
Systemic therapies include any systemic agent given for a cGVHD indication, including extracorporeal photopheresis. Will use Gray's test. Point estimates of new systemic immunosuppressive use will be obtained using cumulative incidence estimates.

Secondary Outcome Measures

Event-free survival
Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.
Overall survival
Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.
Rate of relapse
Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.

Full Information

First Posted
August 10, 2023
Last Updated
October 18, 2023
Sponsor
Fred Hutchinson Cancer Center
Collaborators
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT05996627
Brief Title
Belumosudil for the Pre-emptive Treatment of Patients With Chronic Graft Versus Host Disease
Official Title
Randomized Phase II Study of Belumosudil vs. Placebo for Preemptive Treatment of Chronic Graft Versus Host Disease
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 1, 2024 (Anticipated)
Primary Completion Date
May 31, 2027 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
Sanofi

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 phase II trial compares the effect of belumosudil to a placebo in treating patients with chronic graft versus host disease. Chronic graft versus host disease remains a major complication of stem cell transplantation and can involve multiple organ systems. Belumosudil is a ROCK2 selective inhibitor that works to reduce the immune system response causing the chronic graft versus host disease. Giving belumosudil may better treat patients with chronic graft versus host disease and prevent the need for starting additional immune suppressive medications.
Detailed Description
OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive belumosudil orally (PO) daily (QD) or twice daily (BID) if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive a placebo PO QD or BID if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study. Patients follow up after completion of study medication at 30 days, and at 60 days if 12 cycles are completed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Graft Versus Host Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
The study will be conducted in a double-blinded fashion
Allocation
Randomized
Enrollment
82 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (Belumosudil)
Arm Type
Experimental
Arm Description
Patients receive belumosudil PO QD or BID if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study.
Arm Title
Arm II (Placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive a placebo PO QD or BID if taken with strong CYP3A inducers or proton pump inhibitors for days 1 through 28 of each cycle. Cycles repeat every 28 days for a total of 11 cycles, followed by one cycle of tapering prior to discontinuation, in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study.
Intervention Type
Drug
Intervention Name(s)
Belumosudil
Other Intervention Name(s)
KD 025, KD-025, KD025, Rho-associated Coiled-coil Kinase 2 Inhibitor KD025, ROCK-II Inhibitor KD025, ROCK2 Inhibitor KD025, SLx 2119, SLx-2119, SLx2119
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo blood sample collection
Intervention Type
Other
Intervention Name(s)
Electronic Health Record Review
Intervention Description
Ancillary study
Intervention Type
Drug
Intervention Name(s)
Placebo Administration
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Time to start of subsequent systemic immune suppressive treatment for chronic graft versus host disease (cGVHD)
Description
Systemic therapies include any systemic agent given for a cGVHD indication, including extracorporeal photopheresis. Will use Gray's test. Point estimates of new systemic immunosuppressive use will be obtained using cumulative incidence estimates.
Time Frame
From first dose of study medication to starting a new systemic immunosuppressive agent for cGVHD therapy, up to 12 months
Secondary Outcome Measure Information:
Title
Event-free survival
Description
Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.
Time Frame
From randomization to death, malignancy relapse or addition of a new systemic immune suppressive therapy, up to 12 months or end of study
Title
Overall survival
Description
Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.
Time Frame
Up to 12 months or end of study
Title
Rate of relapse
Description
Point estimates will be obtained using the method of Kaplan and Meier and the log-rank test will be used to assess the difference between treatment groups.
Time Frame
Up to 12 months or end of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: At least one diagnostic or distinctive cGVHD manifestation(s), but patients do not need to meet National Institute of Health (NIH) criteria for cGVHD If eye involvement only, cGVHD must be confirmed on exam by an ophthalmologist or optometrist No new immune suppressive therapy added within preceding 2 weeks prior to study enrollment for any indication Continuation of agents previously given as either GVHD prophylaxis or acute/late acute GVHD therapy are permitted. Modification of dose of these agents for targeting of therapeutic drug levels is permitted, as are decreases in existing prednisone dose based on routine clinical tapering practices. Increases in prednisone are not allowed in the 2 weeks prior to enrollment Age 18 and older Karnofsky performance score >= 70 Able to take oral medications Signed informed consent Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) Total bilirubin =< 1.5 x ULN Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 Female subjects of childbearing potential have a negative serum or urine pregnancy test at screening. Females of childbearing potential are defined as sexually mature females without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, females who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression Sexually active females of childbearing potential enrolled in the study must agree to use two forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control includes: Intrauterine device (IUD) plus one barrier method Stable doses of hormonal contraception for at least 3 months (eg, oral, injectable, implant, transdermal) plus one barrier method 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gel that contain a chemical to kill sperm); or A vasectomized partner For male subjects who are sexually active and who are partners of females of childbearing potential: Agreement to use two forms of contraception as per above and to not donate sperm during the treatment period and for at least 3 months after the last dose of study drug No evidence of active malignancy Exclusion Criteria: Any systemic immune suppressive treatment for cGVHD (topical or local therapies are allowed) Plan to start systemic immune suppressive therapy for cGVHD or increase steroid dose within 14 days after planned start of study medication 0.25 mg/kg/day or higher prednisone dose at time of screening History of non-compliance that in the investigator's opinion would interfere with study participation Uncontrolled psychiatric illness Female subject who is pregnant or breast feeding Previous therapy with belumosudil Known allergy/sensitivity to belumosudil or any other ROCK2 inhibitor Treatment with another investigational agent within 28 days (or 5 half-lives, whichever is greater) of enrollment
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chloe Te
Phone
206-667-4196
Email
cte@fredhutch.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephanie Lee, MD, MPH
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Pidala, MD, PhD
Facility Name
Mass General Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zachariah DeFilipp, MD
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Corey Cutler, MD, MPH
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Doris Ponce, MD
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chloe Te
Phone
206-667-4196
Email
cte@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Stephanie Lee, MD, MPH

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Belumosudil for the Pre-emptive Treatment of Patients With Chronic Graft Versus Host Disease

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