Chronic Graft-Versus-Host DiseasePhase 2NCT01028313
A Study of Panobinostat (LBH589) as Second-Line Therapy in Patients With Chronic Graft-Versus-Host Disease
A Phase 2 study testing LBH589 and Methylprednisolone in people with Chronic Graft-Versus-Host Disease, run by SCRI Development Innovations, LLC at 1 site in United States.
Trial summary
There is a clear need for effective, steroid-sparing agents for the management of chronic graft-versus-host disease (GVHD). Thus, agents like Histone deacetylase (HDAC) inhibitors, with the potential of decreasing pro-inflammatory events leading to GVHD without affecting graft-versus-leukemia (GVL), may have a central… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Graft-Versus-Host Disease
- What is being tested?
- LBH589 and Methylprednisolone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Start not givento not given
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic GvHD following allogeneic HSCT of any source (bone marrow, peripheral blood, or cord blood stem cells), from any donor type (related, unrelated, or mismatched) and with any type of malignancy. Chronic GvHD will be defined according to NIH Consensus Criteria.
- Patients must have had inadequate response to treatment with steroids and calcineurin inhibitors. Patients must have been treated with an initial dose of at least 1 mg/kg/day of methylprednisolone (MP) or equivalent in combination with tacrolimus or cyclosporine and must fulfill the definition of steroid refractoriness or resistance. Steroid refractoriness or resistance will be defined as:
- Lack of any response after 1 month of treatment with MP, including 15 days of at least 0.5 mg/kg/day.
- Worsening of existing GvHD or new organ involvement at any time following one week of initiation of MP at 1 mg/kg/day.
- Reflare or worsening of GvHD at any time during steroid taper.
- Patients should not have received any drug or treatment for chronic GvHD other than steroids and calcineurin inhibitors (i.e., cyclosporine or tacrolimus).
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- Patient must not have evidence of primary disease relapse.
- An ECOG (Eastern Cooperative Oncology Group) performance status of ≤2
- Baseline MUGA or ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥40%.
- No uncontrolled arrhythmias or symptoms of heart disease.
- FEV1, FVC, and DLCO ≥40%.
- Laboratory values as follows:
- white blood cell ≥2500/mm³;
- absolute neutrophil count (ANC) ≥1,000/mm³;
- hemoglobin ≥9.5 g%;
- platelets ≥50,000/mm³;
- total bilirubin <3 x upper limits of normal;
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × the institutional upper limit of normal (ULN);
- creatinine <1.5 × ULN or creatinine clearance ≥ 50 ml/min;
- serum potassium ≥ LLN;
- serum sodium ≥ LLN;
- serum calcium WNL;
- serum phosphorus WNL;
- serum magnesium WNL;
- Patients with elevated alkaline phosphatase due to bone metastasis may be enrolled.
- TSH and free T4 within normal limits (clinically euthyroid patients are permitted to receive thyroid supplements to treat underlying hypothyroidism).
- Age ≥ 18 years, male or female.
- Ability to understand and willingness to sign a written informed consent document.
Who cannot join
- Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer.
- Patients who will need valproic acid for any medical condition during the study or ≤5 days prior to first panobinostat treatment.
- Use of prior immunosuppressants other than steroids and calcineurin inhibitors(i.e. cyclosporine or tacrolimus).
- Chronic active hepatitis or cirrhosis.
- Impaired cardiac function including any of the following:
- Patients with congenital long QT syndrome;
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- Patients with history or presence of sustained ventricular tachyarrhythmias;
- Patients with any history of ventricular fibrillation or Torsades de Pointes;
- Patients with bradycardia defined as HR <50 bpm. Patients with pacemakers are eligible if HR ≥50 bpm.
- Patients with myocardial infarction or unstable angina ≤6 months prior to starting study drug;
- Right bundle branch block plus left anterior hemiblock (bifasicular block);
- Screening ECG with QTc >450 msec;
- Congestive heart failure (CHF) > New York Heart Association (NYHA) Class II (see Appendix D).
- Concomitant use of drugs with a risk of causing Torsades de Pointes (see Appendix A).
- Other concurrent severe and/or uncontrolled medical conditions.
- Any condition that impairs patient's ability to swallow whole pills or gastrointestinal (GI) tract disease that involves an inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV)
Trial locations and contacts
1 site in 1 country.
United States1 site
Tennessee Oncology, PLLC
Nashville, Tennessee, 37023
About this study
Official title: A Phase II Study of Panobinostat (LBH589) as Second-Line Therapy in Patients With Chronic Graft-Versus-Host Disease
There is a clear need for effective, steroid-sparing agents for the management of chronic graft-versus-host disease (GVHD). Thus, agents like Histone deacetylase (HDAC) inhibitors, with the potential of decreasing pro-inflammatory events leading to GVHD without affecting graft-versus-leukemia (GVL), may have a central role in the prevention and treatment of GVHD.
This study will look at the efficacy of panobinostat (LBH589), an HDAC inhibitor, in the treatment of patients with chronic GVHD who have failed corticosteroids. In this group of patients, effective steroid-sparing options are limited and are usually associated with profound immunosuppression and decreased GVL effect.
Read the detailed description
Chronic GVHD is an autoimmune, inflammatory disorder that occurs in the majority of patients who experience acute GVHD. Long-term corticosteroids are still standard therapy for chronic GVHD. Corticosteroids are associated with high morbidity and non-relapse mortality. In addition, corticosteroids are broadly immunosuppressive and can also decrease the GVL effect and increase the incidence of relapse. There is a clear need for effective, steroid-sparing agents for the management of chronic GVHD. Thus, agents like HDAC inhibitors, with the potential of decreasing pro-inflammatory events leading to GVHD without affecting GVL, may have a central role in the prevention and treatment of GVHD.
This study will look at the efficacy of panobinostat (LBH589), an HDAC inhibitor, in the treatment of patients with chronic GVHD who have failed corticosteroids. In this group of patients, effective steroid-sparing options are limited and are usually associated with profound immunosuppression and decreased GVL effect.
- Conditions
- Chronic Graft-Versus-Host Disease
- Being tested
- LBH589, Methylprednisolone
- Keywords
- Chronic Graft-Versus-Host Disease, GVHD, LBH589, Panobinostat
- 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.
LBH589Drug
Also called Panobinostat
20 mg PO three times weekly
Also called Medrol, Depo-Medrol
1 mg/kg/day PO continuously
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Systemic Therapy Receives: Drug: LBH589; Drug: Methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the response rate to panobinostat of patients with cGvHD inadequately treated with steroids and calcineurin inhibitors.
Measured: 30 months
Secondary outcomes (5)
To evaluate the safety and tolerability of panobinostat in patients with cGvHD.
Measured: 30 months
To assess the steroid-sparing capacity of panobinostat (as proportion of patients able to discontinue steroids while receiving, or following therapy with, panobinostat).
Measured: 30 months
To assess changes in quality of life (QOL) after treatment with panobinostat.
Measured: 30 months
To analyze survival at 6 and 12 months after initiation of panobinostat.
Measured: 30 months
To evaluate the relapse rate of the underlying malignancy as well as the occurrence of second malignancies at 6 and 12 months after initiation of panobinostat.
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2009 (estimated)
Why it stopped: A decision was made to not move forward with the study. No participants were enrolled or treated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Graft-Versus-Host DiseaseStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Investigators
- Daniel R Couriel, M.D., Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01028313
- Sponsor's protocol ID
- SCRI BMT 02
- Status last verified
- Feb 2013
- First submitted
- 7 Dec 2009
- Last updated
- 13 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Panobinostat (LBH589) as Second-Line Therapy in Patients With Chronic Graft-Versus-Host Disease
- ClinicalTrials.gov ID
- NCT01028313
- Acronym / sponsor ID
- SCRI BMT 02
- Conditions
- Chronic Graft-Versus-Host Disease
- Keywords
- Chronic Graft-Versus-Host Disease, GVHD, LBH589, Panobinostat
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: A decision was made to not move forward with the study. No participants were enrolled or treated.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Novartis
- First posted
- 9 Dec 2009 (estimated)
- 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.
There is a clear need for effective, steroid-sparing agents for the management of chronic graft-versus-host disease (GVHD). Thus, agents like Histone deacetylase (HDAC) inhibitors, with the potential of decreasing pro-inflammatory events leading to GVHD without affecting graft-versus-leukemia (GVL), may have a central role in the prevention and treatment of GVHD.
This study will look at the efficacy of panobinostat (LBH589), an HDAC inhibitor, in the treatment of patients with chronic GVHD who have failed corticosteroids. In this group of patients, effective steroid-sparing options are limited and are usually associated with profound immunosuppression and decreased GVL effect.
Detailed description
Chronic GVHD is an autoimmune, inflammatory disorder that occurs in the majority of patients who experience acute GVHD. Long-term corticosteroids are still standard therapy for chronic GVHD. Corticosteroids are associated with high morbidity and non-relapse mortality. In addition, corticosteroids are broadly immunosuppressive and can also decrease the GVL effect and increase the incidence of relapse. There is a clear need for effective, steroid-sparing agents for the management of chronic GVHD. Thus, agents like HDAC inhibitors, with the potential of decreasing pro-inflammatory events leading to GVHD without affecting GVL, may have a central role in the prevention and treatment of GVHD.
This study will look at the efficacy of panobinostat (LBH589), an HDAC inhibitor, in the treatment of patients with chronic GVHD who have failed corticosteroids. In this group of patients, effective steroid-sparing options are limited and are usually associated with profound immunosuppression and decreased GVL effect.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: LBH589, Drug: MethylprednisoloneSystemic Therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Chronic GvHD following allogeneic HSCT of any source (bone marrow, peripheral blood, or cord blood stem cells), from any donor type (related, unrelated, or mismatched) and with any type of malignancy. Chronic GvHD will be defined according to NIH Consensus Criteria.
- Patients must have had inadequate response to treatment with steroids and calcineurin inhibitors. Patients must have been treated with an initial dose of at least 1 mg/kg/day of methylprednisolone (MP) or equivalent in combination with tacrolimus or cyclosporine and must fulfill the definition of steroid refractoriness or resistance. Steroid refractoriness or resistance will be defined as:
- Patient must not have evidence of primary disease relapse.
- An ECOG (Eastern Cooperative Oncology Group) performance status of ≤2
- Baseline MUGA or ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥40%.
Key exclusion criteria (16 listed)
- Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer.
- Patients who will need valproic acid for any medical condition during the study or ≤5 days prior to first panobinostat treatment.
- Use of prior immunosuppressants other than steroids and calcineurin inhibitors(i.e. cyclosporine or tacrolimus).
- Chronic active hepatitis or cirrhosis.
- Impaired cardiac function including any of the following:
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 |
|---|---|---|
| LBH589Also: Panobinostat20 mg PO three times weekly | Drug | 1 |
| MethylprednisoloneAlso: Medrol, Depo-Medrol1 mg/kg/day PO continuously | Drug | 1 |
Primary outcome
To assess the response rate to panobinostat of patients with cGvHD inadequately treated with steroids and calcineurin inhibitors.
Time frame: 30 months
5 secondary outcomes
To evaluate the safety and tolerability of panobinostat in patients with cGvHD.
Time frame: 30 months
To assess the steroid-sparing capacity of panobinostat (as proportion of patients able to discontinue steroids while receiving, or following therapy with, panobinostat).
Time frame: 30 months
To assess changes in quality of life (QOL) after treatment with panobinostat.
Time frame: 30 months
To analyze survival at 6 and 12 months after initiation of panobinostat.
Time frame: 30 months
To evaluate the relapse rate of the underlying malignancy as well as the occurrence of second malignancies at 6 and 12 months after initiation of panobinostat.
Time frame: 30 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2013.
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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.
Daniel R Couriel, M.D. study chair
SCRI Development Innovations, LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LBH589 and Methylprednisolone in people with Chronic Graft-Versus-Host Disease, run by SCRI Development Innovations, LLC 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 28 inclusion and 16 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: withdrawn, as of the sponsor's last update on 13 Feb 2013. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
To assess the response rate to panobinostat of patients with cGvHD inadequately treated with steroids and calcineurin inhibitors. (time frame: 30 months). 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 13 Feb 2013.