Study of Ruxolitinib for Acute and Chronic Graft Versus Host Disease

NCT05121142 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2021-0167
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

While hematopoietic stem cell transplant (HSCT) is an effective therapy, graft versus host disease (GVHD) is the most significant complication after HSCT. Both acute GVHD and chronic GVHD are leading causes of non-relapse morbidity and mortality. Patients with solid organ transplants may participate in this study as well because these patients occasionally develop acute GVHD, which is biologically similar to acute GVHD after an HSCT. Acute graft versus host disease usually occurs within the first 100 days of transplant and can involve the skin, gut, or liver. Chronic graft versus host disease usually occurs after the first 100 days of transplant and can involve skin, eyes, mouth, joints, liver, intestines commonly. These two diseases are different, but both happen due to the imbalance of the donor immune system in the host. The purpose of this research is to learn more about ruxolitinib as a treatment for both acute and chronic GVHD. Specifically, the investigators would like to learn more about the pharmacokinetics (PK - the process of absorption, distribution, metabolism, and elimination from the body - meaning how the drug moves through the body) and the pharmacodynamics (PD - the body's biological response to the drug) of ruxolitinib.

Conditions

Acute-graft-versus-host Disease; Chronic Graft-versus-host-disease; Solid Organ Transplant

Outcome Measures

Primary Outcomes (4)

• Cmax of ruxolitinib in existing patients with chronic GVHD (Arm 1)

  Maximum Plasma Concentration of ruxolitinib

  1 week

• Cmax of ruxolitinib in patients with acute GVHD (Arm 2)

  Maximum Plasma Concentration of ruxolitinib

  30 days

• Cmax of ruxolitinib in patients with new onset chronic GVHD (Arm 3)

  Maximum Plasma Concentration of ruxolitinib

  6 months

• To measure phosphorylation of STAT5 on lymphocytes as a functional measure of JAK inhibition (Arms 1, 2, and 3)

  A blood sample will be collected at the specified time point and pharmacodynamics will be measured by PSTAT5

  Approximately 2 hours after the ruxolitinib dose

Secondary Outcomes (18)

• Number of participants with overall survival (Arm 3)

  6 months after ruxolitinib initiation

• Number of participants with complete response to ruxolitinib (Arm 2)

  30 days after ruxolitinib initiation

• Number of participants with partial response to ruxolitinib (Arm 2)

  30 days after ruxolitinib initiation

• Number of participants with no response to ruxolitinib (Arm 2)

  30 days after ruxolitinib initiation

• Number of participants with response to ruxolitinib (Arm 3)

  6 months after ruxolitinib initiation

Study Arms (3)

Arm 1: Existing patients with chronic GVHD

NO INTERVENTION

Participants with established diagnosis of chronic GVHD and currently on treatment with ruxolitinib for chronic GVHD for at least 3 weeks. Participants in this arm are receiving ruxolitinib clinically and will not receive ruxolitinib as part of this research study.

Arm 2: Acute GVHD ages 0-<12 years

EXPERIMENTAL

Participants with acute GVHD will receive ruxolitinib on this arm.

Drug: Ruxolitinib

Arm 3: New onset chronic GVHD ages 0-≤18 years

EXPERIMENTAL

Participants with new onset chronic GVHD will receive ruxolitinib on this arm.

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

Ruxolitinib will be given by mouth or enteral tube (if applicable).

Arm 2: Acute GVHD ages 0-<12 years; Arm 3: New onset chronic GVHD ages 0-≤18 years

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Established diagnosis of chronic GVHD (all grades eligible)
• Currently on treatment with ruxolitinib for chronic GVHD for a minimum of 3 weeks
• No changes in doses of ruxolitinib or concurrent azoles (if present) one week prior to obtaining ruxolitinib levels
• Ages eligible for enrollment (0-≤18 years at time of enrollment)

You may not qualify if:

• Clinical presentation resembling overlap syndrome with both acute and chronic GVHD features
• ARM 2
• Ages \<12 years status post allogeneic hematopoietic stem cell transplant or solid organ transplant
• Any underlying diagnoses, preparative regimen, stem cell source or acute GVHD prophylaxis are eligible
• Diagnosis of acute GVHD which is refractory to steroids (defined as lack of improvement to 2 mg/kg/day of methylprednisolone or bioequivalent oral steroids, for 7 days or progression of acute GVHD within 72 hours at 2 mg/kg/day of Methylprednisolone or bioequivalent oral doses)
• Able to take enteral medications
• Clinically diagnosed Grades II to IV acute GVHD as per modified Glucksberg criteria occurring after allogeneic HSCT requiring systemic immune suppressive therapy. Biopsy of involved organs with acute GVHD is encouraged but not required for study enrollment.
• Blood counts at decision to initiate ruxolitinib: absolute neutrophil count (ANC) \> 1000/mm3\* AND platelets ≥ 20,000/mm3 (\*Use of growth factor supplementation and transfusion support is allowed to achieve these above defined hematological parameters)
• Estimated GFR by cystatin C of \>30 mL/min
• Prior systemic treatments for acute GVHD are allowed. Once ruxolitinib is initiated, no further doses of these agents will be allowed.
• Calcineurin inhibitors are allowed throughout the duration of study and may be discontinued per treating physician discretion. Additionally dose adjustments to maintain target blood levels of calcineurin inhibitors may proceed per routine clinical practice.
• Clinical presentation resembling de novo chronic GVHD or GVHD overlap syndrome with both acute and chronic GVHD features
• Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
• Evidence of uncontrolled viral reactivation (Adenovirus, CMV, EBV, BK virus). If patients are on appropriate antiviral therapy or have received virus specific T-cells (either donor derived or third-party) then the viral reactivation is not considered uncontrolled.
• Presence of relapsed primary malignancy.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Officials

• Pooja Khandelwal, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: November 16, 2021
• Study Start: October 27, 2021
• Primary Completion: May 13, 2023
• Study Completion: May 13, 2023
• Last Updated: January 16, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)