Acute-graft-versus-host DiseasePhase 1NCT05121142
Study of Ruxolitinib for Acute and Chronic Graft Versus Host Disease
A Phase 1 study testing Ruxolitinib in people with Acute-graft-versus-host Disease and Chronic Graft-versus-host-disease, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Acute-graft-versus-host Disease, Chronic Graft-versus-host-disease, Solid Organ Transplant
- What is being tested?
- Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Oct 2021to 13 May 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
- 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
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- 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.
- 0-≤18 years of age are eligible
- Any underlying diagnosis, preparative regimen, stem cell source or prior acute GVHD prophylaxis are eligible
- Diagnosis of chronic GVHD as per 2014 NIH consensus criteria (any organ involvement is eligible)
- Any GVHD global severity is eligible
- Patients may have received methylprednisolone or oral bioequivalent steroids at a dose of 1 mg/kg/day (or greater) for up to 28 days prior to enrollment but may be enrolled anytime between diagnosis of chronic GVHD and day 28 of systemic steroids
- Concurrent local therapies ( including but not limited to topical steroids, topical calcipotriene, ocular drops such as restasis, autologous serum eye drops, artificial tears, triamcinolone ointment for vulvar GVHD, Fluticasone Azithromycin and Singulair) are allowed at anytime while on ruxolitinib . Additional therapies may also be considered with PI review and approval
- As children may not meet criteria for lung GVHD due to inability to perform PFTs we will establish the diagnosis of lung GVHD for children as defined by any of the following criteria listed below. However, the participants do not need to have lung involvement to be eligible to receive ruxolitinib.
- >10% decrease in FEV1 or FVC from baseline or 25% of FEF 25-75
- Active GVHD in another organ system + pulmonary symptoms (Tachypnea without wheezing, new oxygen requirement, cough)
- Increased R5 by 50% by Impulse oscillometry
- Air trapping on high resolution CT scan, small airway thickening, or bronchiectasis in the absence of infection
- Negative urine or serum pregnancy test for females of childbearing age
- Estimated GFR by cystatin C > 30 mL/min
- Able to take enteral medications
Who cannot join
- Clinical presentation resembling overlap syndrome with both acute and chronic GVHD features
- ARM 2
- 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.
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- ARM 3
- Clinical presentation resembling 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: Pharmacokinetics and Pharmacodynamic Study of Ruxolitinib for the Management of Acute and Chronic Graft Versus Host Disease
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
- Being tested
- Ruxolitinib
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Ruxolitinib will be given by mouth or enteral tube (if applicable).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax of ruxolitinib in existing patients with chronic GVHD (Arm 1)
Maximum Plasma Concentration of ruxolitinib
Measured: 1 week
Cmax of ruxolitinib in patients with acute GVHD (Arm 2)
Maximum Plasma Concentration of ruxolitinib
Measured: 30 days
Cmax of ruxolitinib in patients with new onset chronic GVHD (Arm 3)
Maximum Plasma Concentration of ruxolitinib
Measured: 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
Measured: Approximately 2 hours after the ruxolitinib dose
Secondary outcomes (18)
Number of participants with overall survival (Arm 3)
Measured: 6 months after ruxolitinib initiation
Number of participants with complete response to ruxolitinib (Arm 2)
Complete response is defined as resolution of acute GVHD
Measured: 30 days after ruxolitinib initiation
Number of participants with partial response to ruxolitinib (Arm 2)
Partial response is defined as improvement in stage of at least one organ involved in acute GVHD without worsening in additional organs
Measured: 30 days after ruxolitinib initiation
Number of participants with no response to ruxolitinib (Arm 2)
No response is defined as lack of improvement or worsening of acute GVHD
Measured: 30 days after ruxolitinib initiation
Number of participants with response to ruxolitinib (Arm 3)
Response is defined as resolution of chronic GVHD in at least one organ without worsening in additional organs
Measured: 6 months after ruxolitinib initiation
Number of participants with relapse free survival at 6 months (Arm 3)
Measured: 6 months after ruxolitinib initiation
Number of participants with relapse free survival at 6 months (Arm 1)
Relapse free survival at 6 months for participants on Arm 1 only if participant has been on ruxolitinib clinically for 6 months
Measured: 6 months after ruxolitinib initiation
Incidence of infections (Arm 1)
Infections defined as bacterial, parasitic, fungal, new viral reactivation or disease
Measured: through study completion, average of 7 days
Incidence of infections (Arm 2)
Infections defined as bacterial, parasitic, fungal, new viral reactivation or disease
Measured: 30 days after ruxolitinib initiation
Incidence of infections (Arm 3)
Infections defined as bacterial, parasitic, fungal, new viral reactivation or disease
Measured: 6 months after ruxolitinib initiation
Incidence of known side effects (Arm 1)
Known side effects are defined as the side effects included in the Investigator's Brochure
Measured: through study completion, average of 7 days
Incidence of known side effects (Arm 2)
Known side effects are defined as the side effects included in the Investigator's Brochure
Measured: 30 days after ruxolitinib initiation
Incidence of known side effects (Arm 3)
Known side effects are defined as the side effects included in the Investigator's Brochure
Measured: 6 months after ruxolitinib initiation
Incidence of unknown side effects (Arm 1)
Unknown side effects are defined as the side effects not included in the Investigator's Brochure
Measured: through study completion, average of 7 days
Incidence of unknown side effects (Arm 2)
Unknown side effects are defined as the side effects not included in the Investigator's Brochure
Measured: 30 days after ruxolitinib initiation
Incidence of unknown side effects (Arm 3)
Unknown side effects are defined as the side effects not included in the Investigator's Brochure
Measured: 6 months after ruxolitinib initiation
Number of participants who were weaned off steroids (Arm 2)
Participants will be considered weaned off steroids if the steroid dose has been decreased
Measured: 30 days after ruxolitinib initiation
Number of participants who were weaned off steroids (Arm 3)
Participants will be considered weaned off steroids if the steroid dose has been decreased
Measured: 6 months after ruxolitinib initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2021
- Study start27 Oct 2021
- Primary completion13 May 2023
- Study completion13 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute-graft-versus-host DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pooja Khandelwal, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05121142
- Sponsor's protocol ID
- 2021-0167
- Status last verified
- Jan 2024
- First submitted
- 1 Sep 2021
- Last updated
- 16 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Pharmacodynamic Study of Ruxolitinib for the Management of Acute and Chronic Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT05121142
- Acronym / sponsor ID
- 2021-0167
- Conditions
- Acute-graft-versus-host Disease, Chronic Graft-versus-host-disease, Solid Organ Transplant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- 27 Oct 2021 (actual)
- Primary completion
- 13 May 2023 (actual)
- Study completion
- 13 May 2023 (actual)
- First posted
- 16 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: RuxolitinibParticipants with acute GVHD will receive ruxolitinib on this arm. |
| Arm 3: New onset chronic GVHD ages 0-≤18 years | Experimental | Drug: RuxolitinibParticipants with new onset chronic GVHD will receive ruxolitinib on this arm. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (27 listed)
- 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)
- Ages <12 years status post allogeneic hematopoietic stem cell transplant or solid organ transplant
Key exclusion criteria (11 listed)
- Clinical presentation resembling overlap syndrome with both acute and chronic GVHD features
- ARM 2
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RuxolitinibRuxolitinib will be given by mouth or enteral tube (if applicable). | Drug | Arm 2: Acute GVHD ages 0-<12 years, Arm 3: New onset chronic GVHD ages 0-≤18 years |
Primary outcome
Cmax of ruxolitinib in existing patients with chronic GVHD (Arm 1)
Time frame: 1 week
Maximum Plasma Concentration of ruxolitinib
Cmax of ruxolitinib in patients with acute GVHD (Arm 2)
Time frame: 30 days
Maximum Plasma Concentration of ruxolitinib
Cmax of ruxolitinib in patients with new onset chronic GVHD (Arm 3)
Time frame: 6 months
Maximum Plasma Concentration of ruxolitinib
To measure phosphorylation of STAT5 on lymphocytes as a functional measure of JAK inhibition (Arms 1, 2, and 3)
Time frame: Approximately 2 hours after the ruxolitinib dose
A blood sample will be collected at the specified time point and pharmacodynamics will be measured by PSTAT5
18 secondary outcomes
Number of participants with overall survival (Arm 3)
Time frame: 6 months after ruxolitinib initiation
Number of participants with complete response to ruxolitinib (Arm 2)
Time frame: 30 days after ruxolitinib initiation
Number of participants with partial response to ruxolitinib (Arm 2)
Time frame: 30 days after ruxolitinib initiation
Number of participants with no response to ruxolitinib (Arm 2)
Time frame: 30 days after ruxolitinib initiation
Number of participants with response to ruxolitinib (Arm 3)
Time frame: 6 months after ruxolitinib initiation
Number of participants with relapse free survival at 6 months (Arm 3)
Time frame: 6 months after ruxolitinib initiation
Number of participants with relapse free survival at 6 months (Arm 1)
Time frame: 6 months after ruxolitinib initiation
Incidence of infections (Arm 1)
Time frame: through study completion, average of 7 days
Incidence of infections (Arm 2)
Time frame: 30 days after ruxolitinib initiation
Incidence of infections (Arm 3)
Time frame: 6 months after ruxolitinib initiation
Incidence of known side effects (Arm 1)
Time frame: through study completion, average of 7 days
Incidence of known side effects (Arm 2)
Time frame: 30 days after ruxolitinib initiation
Incidence of known side effects (Arm 3)
Time frame: 6 months after ruxolitinib initiation
Incidence of unknown side effects (Arm 1)
Time frame: through study completion, average of 7 days
Incidence of unknown side effects (Arm 2)
Time frame: 30 days after ruxolitinib initiation
Incidence of unknown side effects (Arm 3)
Time frame: 6 months after ruxolitinib initiation
Number of participants who were weaned off steroids (Arm 2)
Time frame: 30 days after ruxolitinib initiation
Number of participants who were weaned off steroids (Arm 3)
Time frame: 6 months after ruxolitinib initiation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pooja Khandelwal, MD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ruxolitinib in people with Acute-graft-versus-host Disease and Chronic Graft-versus-host-disease, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax of ruxolitinib in existing patients with chronic GVHD (Arm 1) (time frame: 1 week). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2024.