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| ID | Type | Description | Link |
|---|---|---|---|
| CLBH589US100T | Other Identifier | Novartis |
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| Name | Class |
|---|---|
| Novartis | INDUSTRY |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Panobinostat | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 100 days post transplant |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lia Perez, M.D. | H. Lee Moffitt Cancer Center and Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | 33612 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37189240 | Derived | 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. | |
| 34242388 | Derived | Perez 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. |
| Label | URL |
|---|---|
| Moffitt Cancer Center Clinical Trials website | View source |
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Participants recruited between March 2016 and August 2018
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| ID | Title | Description |
|---|---|---|
| FG000 | Panobinostat (PANO) Therapy | Participants treated with standard of care chemotherapy agents prior to their allogeneic hematopoietic cell transplant. For Graft Versus Host Disease (GVHD) prevention, participants received PANO, Sirolimus and Tacrolimus. GVHD graded using NIH criteria, scores of 0-3 per area of involvement (e.g; skin, liver and gut) 0 being no symptoms and 3 being symptomatic, over 50% of waking hours in bed, ECOG 3-4. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Panobinostat (PANO) Therapy | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 100 days post transplant |
|
3 years, 6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Panobinostat (PANO) Therapy | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chest pain - cardiac | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lung Infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lia E. Perez, MD | Moffitt Cancer Center | 813-745-3665 | Lia.Perez@moffitt.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 12, 2018 | Dec 5, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| D006402 | Hematologic Diseases |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000077767 | Panobinostat |
| D020123 | Sirolimus |
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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|
|
| Sirolimus | Drug | 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. |
|
|
| Tacrolimus | Drug | 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. |
|
|
| 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. | 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. | 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. | 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. | 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. | 1 year |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 100 days post transplant |
|
|
|
| Secondary | 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. | Participants with stable engraftment were analyzed | Posted | Median | 95% Confidence Interval | days | 100 days post transplant |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 1 year |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 1 year |
|
|
|
| Secondary | 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. | Posted | Number | percentage of participants | 1 year |
|
|
|
| Secondary | 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. | Posted | Number | percentage of participants | 1 year |
|
|
|
| 2 |
| 39 |
| 12 |
| 39 |
| 32 |
| 39 |
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sinus disorder | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders -Other | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment | skin infection |
|
| Confusion | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lung infection | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Enterocolitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Immune system disorders -Other | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Allergic reaction | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pulmonary edema | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Akathisia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Edema limbs | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Portal hypertension | Hepatobiliary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased -Transiminitis | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Hepatobiliary disorders - other | Hepatobiliary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Appendicitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Encephalitis infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Confusion | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pulmonary edema | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hallucinations | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Papulopustular rash | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Myelitis | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Floaters | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Weight loss | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Edema limbs | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Bullous dermatitis | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Akathisia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Periorbital edema | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Appendicitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Immune system disorders -Other | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D006880 |
| Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D018942 | Macrolides |
| D007783 | Lactones |