Graft Versus Host DiseasePhase 2NCT02588339
Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention
A Phase 2 study testing Panobinostat, Sirolimus and Tacrolimus in people with Graft Versus Host Disease and GVHD, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
This study will test PANO in combination with tacrolimus/sirolimus (TAC/SIR) for acute GVHD prevention. The purpose of this study is to determine if Panobinostat (PANO) when used in combination with sirolimus and tacrolimus will help reduce the incidence of Graft-vs-host disease (GVHD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Versus Host Disease, GVHD
- What is being tested?
- Panobinostat, Sirolimus and Tacrolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Mar 2016to 13 Jul 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age ≥ 18 years or older at time of enrollment
- Signed informed consent
- Hematologic disorder requiring allogeneic hematopoietic cell transplantation
- Left ventricular ejection fraction (LVEF) ≥ 45% by multiple uptake gated acquisition (MUGA) scan or echocardiogram
- Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusing lung capacity oxygenation (DLCO) adjusted ≥ 50% of predicted values on pulmonary function tests
- Transaminases (AST, ALT) < 3 times upper limit of normal (ULN) values
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- Creatinine clearance calculated ≥ 50 mL/min
- Karnofsky Performance Status Score ≥ 60%.
- Human leukocyte antigen (HLA) matched 8/8 (A, B, C, DRB1) related or unrelated donor
Who cannot join
- Active infection not controlled with appropriate antimicrobial therapy
- HIV, hepatitis B (HBcAb positive but HBsAg negative with undetectable viral load are eligible), or hepatitis C infection
- Sorror's co-morbidity factors with total score > 4. Important modification to co-morbidity index calculation: DLCO adjusted will not be included in assessment of pulmonary risk, except those patients with DLCO adjusted < 50% who are excluded from the trial.
- Anti-thymocyte globulin (ATG) as part of the conditioning regimen
- Cyclophosphamide as part of the conditioning regimen or for GVHD prophylaxis
- Pregnancy
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- Histone deacetylase (HDAC), DAC, HSP90 inhibitors or valproic acid for the treatment of cancer within 30 days
- Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first PANO treatment
- Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: Any history of ventricular fibrillation or torsade de pointes; Bradycardia defined as heart rate (HR)< 45 bpm (Patients with pacemakers are eligible if HR ≥ 45 bpm); Screening electrocardiogram (ECG) with a QTcF > 480 msec; Right bundle branch block + left anterior hemiblock (bifascicular block); Patients with myocardial infarction or unstable angina ≤ 12 months prior to starting study drug; Other clinically significant heart disease (e.g., New York Heart Association (NYHA) class III or IV , uncontrolled hypertension) as per discretion of principal investigator and/or treating physician; Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug with the exception of drugs listed on Appendix B of study documents that are required for hematopoietic cell transplantation (HCT) patients.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Phase II Trial Evaluating the Use of a Histone Deacetylase Inhibitor Panobinostat for Graft Versus Host Disease (GVHD) Prevention
This study will test PANO in combination with tacrolimus/sirolimus (TAC/SIR) for acute GVHD prevention. The purpose of this study is to determine if Panobinostat (PANO) when used in combination with sirolimus and tacrolimus will help reduce the incidence of Graft-vs-host disease (GVHD).
- Conditions
- Graft Versus Host Disease, GVHD
- Being tested
- Panobinostat, Sirolimus, Tacrolimus
- Keywords
- Hematologic disorder, allogeneic hematopoietic cell transplantation
- Medical subject headings
- Graft vs Host Disease, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanobinostatDrug
Also called PANO, Farydak, LBH-589
Panobinostat (PANO) will begin 5 days (Day -5) before transplant day (Day 0). All participants will take PANO by mouth once a day, three times a week (48 hours apart), every week for 26 weeks (approximately 6 months). PANO will be provided by Novartis as 5-mg pink gelatin capsules.
SirolimusDrug
Also called SIR, Rapamune
Sirolimus will be given the day before transplant and continued daily for at least one year. SIR will be administered starting on day -1 and thereafter. Dosing will be adjusted to maintain therapeutic targets per Moffitt institutional standards.
TacrolimusDrug
Also called TAC, Prograf
Tacrolimus as an infusion or as a pill will begin 3 days before transplant (day -3) and following Moffitt institutional guidelines for dosing. Tacrolimus will be given for at least 50 days and participants will remain on Tacrolimus for as long as it is necessary per standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Panobinostat (PANO) Therapy | Experimental | Participants will be treated with standard of care chemotherapy agents prior to their allogeneic hematopoietic cell transplant. For Graft Versus Host Disease (GVHD) prevention, participants will receive PANO, Sirolimus and Tacrolimus. Receives: Drug: Panobinostat; Drug: Sirolimus; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Stratified by Acute Graft Versus Host Disease GVHD Stage
Cumulative incidence of acute GVHD grades II-IV by day 100. Investigators will consider ≥43% incidence of grade II-IV aGVHD not acceptable. Investigators will use 23% incidence rate of GVHD as target. GVHD severity stage and grading and distribution will be measured weekly from day of transplant to day 90 +/- 14 using standard scoring system. Stage of GVHD will be given for each site of involvement (e.g. skin, liver, and gut), as well as a composite score for overall acute GVHD grade. Pathologic confirmation of aGVHD will be dictated by usual clinical practice, and not mandated by this protocol.
Measured: 100 days post transplant
Secondary outcomes (6)
Number of Participants Stratified by Chronic Graft Versus Host Disease (GVHD) Stage
GVHD with onset after 100 days post-HCT with presence of at least one diagnostic manifestation of chronic c-GVHD or distinct manifestation confirmed by biopsy or other relevant tests (e.g., PFT). Classified as: 1- Classic chronic GVHD - meets criteria for chronic GVHD and has no features consistent with aGVHD or 2-Overlap syndrome - features of acute and chronic GVHD exist together. C-GVHD will be measured prospectively in all participants on days 90+/-14 , 120 +/- 14, 150 +/- 14, 180+/- 14, 270+/- 30, and 365 +/- 30 as per standardized scoring system.
Measured: 100 days post transplant
Time to Stable Engraftment
Stable engraftment for white blood count (WBC) is defined as a sustained absolute neutrophil count > 500 over 3 days without cytokine support. Stable platelet engraftments is defined as count of > 20,000 over 7 days without transfusion support. Time to engraftment is defined as time from day 0 to day of sustained engraftment per above criteria for both platelets and WBC.
Measured: 100 days post transplant
Number of Participants With Primary Disease Relapse
Incidence of primary disease relapse and non-relapse related death will be reported per standard definitions. These will be treated as competing risk events.
Measured: 1 year
Number of Participants With Non-relapse Mortality
Incidence of primary disease relapse and non-relapse related death will be reported per standard definitions. These will be treated as competing risk events. Non-relapse death is defined as death in continuous remission from primary disease requiring transplantation.
Measured: 1 year
Percentage of Participants With Overall Survival (OS)
Overall survival: Time from transplant date to death from any cause. Time-to-event data such as overall survival is measured from the date of transplantation. OS will be analyzed using the Kaplan-Meier method.
Measured: 1 year
Percentage of Participants With Relapse-free Survival (RFS)
Relapse-free survival: Time from transplant date to death or primary disease relapse. Time-to-event data such as relapse-free survival is measured from the date of transplantation. RFS will be analyzed using the Kaplan-Meier method.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2015 (estimated)
- Study start4 Mar 2016
- Primary completion7 Dec 2018
- Study completion13 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Lia Perez, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02588339
- Sponsor's protocol ID
- MCC-18374
- Other IDs
- CLBH589US100T
- Status last verified
- Jul 2021
- First submitted
- 26 Oct 2015
- Last updated
- 21 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Lakshmanan AP, Deola S, Terranegra A. The Promise of Precision Nutrition for Modulation of the Gut Microbiota as a Novel Therapeutic Approach to Acute Graft-versus-host Disease. Transplantation. 2023 Dec 1;107(12):2497-2509. doi: 10.1097/TP.0000000000004629. Epub 2023 May 16.
PubMed 37189240Perez L, Fernandez H, Kharfan-Dabaja M, Khimani F, Betts B, Mishra A, Ayala E, Locke FL, Ochoa-Bayona L, Nieder M, Pidala J, Achille A, Powers J, Sahakian E, Thapa R, Wang X, Anasetti C. A phase 2 trial of the histone deacetylase inhibitor panobinostat for graft-versus-host disease prevention. Blood Adv. 2021 Jul 13;5(13):2740-2750. doi: 10.1182/bloodadvances.2021004225.
PubMed 34242388
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial Evaluating the Use of a Histone Deacetylase Inhibitor Panobinostat for Graft Versus Host Disease (GVHD) Prevention
- ClinicalTrials.gov ID
- NCT02588339
- Acronym / sponsor ID
- MCC-18374
- Conditions
- Graft Versus Host Disease, GVHD
- Keywords
- Hematologic disorder, allogeneic hematopoietic cell transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 4 Mar 2016 (actual)
- Primary completion
- 7 Dec 2018 (actual)
- Study completion
- 13 Jul 2021 (actual)
- First posted
- 27 Oct 2015 (estimated)
- Results
- Posted 3 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test PANO in combination with tacrolimus/sirolimus (TAC/SIR) for acute GVHD prevention. The purpose of this study is to determine if Panobinostat (PANO) when used in combination with sirolimus and tacrolimus will help reduce the incidence of Graft-vs-host disease (GVHD).
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Panobinostat (PANO) Therapy | Experimental | Drug: Panobinostat, Drug: Sirolimus, Drug: TacrolimusParticipants will be treated with standard of care chemotherapy agents prior to their allogeneic hematopoietic cell transplant. For Graft Versus Host Disease (GVHD) prevention, participants will receive PANO, Sirolimus and Tacrolimus. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥ 18 years or older at time of enrollment
- Signed informed consent
- Hematologic disorder requiring allogeneic hematopoietic cell transplantation
- Left ventricular ejection fraction (LVEF) ≥ 45% by multiple uptake gated acquisition (MUGA) scan or echocardiogram
- Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusing lung capacity oxygenation (DLCO) adjusted ≥ 50% of predicted values on pulmonary function tests
Key exclusion criteria (9 listed)
- Active infection not controlled with appropriate antimicrobial therapy
- HIV, hepatitis B (HBcAb positive but HBsAg negative with undetectable viral load are eligible), or hepatitis C infection
- Sorror's co-morbidity factors with total score > 4. Important modification to co-morbidity index calculation: DLCO adjusted will not be included in assessment of pulmonary risk, except those patients with DLCO adjusted < 50% who are excluded from the trial.
- Anti-thymocyte globulin (ATG) as part of the conditioning regimen
- Cyclophosphamide as part of the conditioning regimen or for GVHD prophylaxis
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 |
|---|---|---|
| PanobinostatAlso: PANO, Farydak, LBH-589Panobinostat (PANO) will begin 5 days (Day -5) before transplant day (Day 0). All participants will take PANO by mouth once a day, three times a week (48 hours apart), every week for 26 weeks (approximately 6 months). PANO will be provided by Novartis as 5-mg pink gelatin capsules. | Drug | Panobinostat (PANO) Therapy |
| SirolimusAlso: SIR, RapamuneSirolimus will be given the day before transplant and continued daily for at least one year. SIR will be administered starting on day -1 and thereafter. Dosing will be adjusted to maintain therapeutic targets per Moffitt institutional standards. | Drug | Panobinostat (PANO) Therapy |
| TacrolimusAlso: TAC, PrografTacrolimus as an infusion or as a pill will begin 3 days before transplant (day -3) and following Moffitt institutional guidelines for dosing. Tacrolimus will be given for at least 50 days and participants will remain on Tacrolimus for as long as it is necessary per standard of care. | Drug | Panobinostat (PANO) Therapy |
Primary outcome
Number of Participants Stratified by Acute Graft Versus Host Disease GVHD Stage
Time frame: 100 days post transplant
Cumulative incidence of acute GVHD grades II-IV by day 100. Investigators will consider ≥43% incidence of grade II-IV aGVHD not acceptable. Investigators will use 23% incidence rate of GVHD as target. GVHD severity stage and grading and distribution will be measured weekly from day of transplant to day 90 +/- 14 using standard scoring system. Stage of GVHD will be given for each site of involvement (e.g. skin, liver, and gut), as well as a composite score for overall acute GVHD grade. Pathologic confirmation of aGVHD will be dictated by usual clinical practice, and not mandated by this protocol.
6 secondary outcomes
Number of Participants Stratified by Chronic Graft Versus Host Disease (GVHD) Stage
Time frame: 100 days post transplant
Time to Stable Engraftment
Time frame: 100 days post transplant
Number of Participants With Primary Disease Relapse
Time frame: 1 year
Number of Participants With Non-relapse Mortality
Time frame: 1 year
Percentage of Participants With Overall Survival (OS)
Time frame: 1 year
Percentage of Participants With Relapse-free Survival (RFS)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37189240Lakshmanan AP, Deola S, Terranegra A. The Promise of Precision Nutrition for Modulation of the Gut Microbiota as a Novel Therapeutic Approach to Acute Graft-versus-host Disease. Transplantation. 2023 Dec 1;107(12):2497-2509. doi: 10.1097/TP.0000000000004629. Epub 2023 May 16.
- Derived from this study: PubMed 34242388Perez L, Fernandez H, Kharfan-Dabaja M, Khimani F, Betts B, Mishra A, Ayala E, Locke FL, Ochoa-Bayona L, Nieder M, Pidala J, Achille A, Powers J, Sahakian E, Thapa R, Wang X, Anasetti C. A phase 2 trial of the histone deacetylase inhibitor panobinostat for graft-versus-host disease prevention. Blood Adv. 2021 Jul 13;5(13):2740-2750. doi: 10.1182/bloodadvances.2021004225.
- Moffitt Cancer Center Clinical Trials websiteLink provided by the sponsor.
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Graft vs Host Disease
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.
Lia Perez, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
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 Panobinostat, Sirolimus and Tacrolimus in people with Graft Versus Host Disease and GVHD, run by H. Lee Moffitt Cancer Center and Research Institute 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 9 inclusion and 9 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 21 Jul 2021. 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?
Yes. Results are posted in the registry (first posted 3 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants Stratified by Acute Graft Versus Host Disease GVHD Stage (time frame: 100 days post transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02588339, which also lists 2 linked publications.
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 21 Jul 2021.