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This is a single arm open label phase II clinical trial. Adult patients with hematological malignancies undergoing allogeneic HSCT from matched-related or unrelated donor are eligible for the study if they meet the standard criteria defined in the investigator's institutional standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Patients will receive reduced-intensity or myeloablative conditioning regimen of fludarabine, busulfan, and rabbit anti-thymocyte globulin (rATG). Patients will receive PTCyBor as GvHD prophylaxis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cyclophosphamide and Bortezomib | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bortezomib | Drug | 1.3 mg/m2 IV 6 hours after graft infusion and 72 hours thereafter. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Experience Acute GvHD | Rate of acute GvHD post-transplant. All participants that received a transplant and received any prophylactic treatment will be included in the analysis. | Day 120 Post-Transplant |
| Percentage of Participants Who Experience Moderate to Severe Chronic GvHD | Rate of chronic GvHD post-transplant. All participants that received a transplant and received any prophylactic treatment will be included in the analysis. | Day 365 Post-Transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Primary Graft Failure | Incidence of graft failure will be calculated from date of transplant to failure for all patients who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment. Graft failure is defined as failure to achieve neutrophil engraftment by day 28 post-transplant or lack of donor chimerism > 50% by day 45 post-transplant not due to the underlying malignancy. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ahmad Al-Homsi, MD | New York Langone Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New York University School of Medicine | New York | New York | 10016 | United States |
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).Upon reasonable request is likely the most appropriate as well will report on incidental findings (i.e. infections) that may impact transplant.
Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
Requests should be directed to Ankeeta.Joshi@nyulangone.org To gain access, data requestors will need to sign a data access agreement.
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23 participants were consented. 2 of these participants did not initiate the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cyclophosphamide and Bortezomib | Bortezomib: 1.3 mg/m2 IV 6 hours after graft infusion and 72 hours thereafter. Cyclophosphamide: 50 mg/kg IV over 2 hours on Day +3 and +4 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Oct 29, 2019 |
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| Cyclophosphamide | Drug | 50 mg/kg IV over 2 hours on Day +3 and +4 |
|
| Day 45 Post-Transplant |
| Incidence of Poor Graft Function | Incidence of poor graft function will be calculated from date of transplant to failure for all patients who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment. Poor graft function is defined by at least 2 of the following 3 criteria: Hemoglobin < 8 g/dL, ANC < 0.5 109/L, and platelets < 20 109/L. The cytopenia must be unexplained (such as by disease relapse) and unresponsive to cytokines and must last at least 4 weeks. | Day 30 Post-Transplant |
| Incidence of Secondary Graft Failure | Incidence of secondary graft failure is evaluated after engraftment is achieved; this outcome is calculated from date of engraftment for all patients with engraftment. Secondary graft failure is defined as poor graft function associated with donor chimerism < 5%. | Day 730 Post-Transplant |
| Treatment Related Mortality (TRM) | Number of participant deaths not attributable to disease relapse or progression . This outcome is analyzed based on participants that who received a transplant with any prophylactic treatment and for all patients who received a transplant and completed prophylactic treatment. | Day 730 Post-Transplant |
| Relapse Rate (RR) | Percentage of participants in whom the disease for which transplant is performed is evident by methods of disease detection after transplant. This outcome is analyzed for all patients who received a transplant and for all transplanted patients that completed treatment. | Day 730 Post-Transplant |
| Graft Versus Host Disease Relapse Free Survival (GRFS) | Percentage of participants who are without reported GvHD III-IV acute GvHD, chronic GvHD requiring systemic therapy and have not experienced relapse or death after transplant. | Day 730 Post-Transplant |
| Overall Survival (OS) | Percentage of participants alive at the end of the study's evaluation period. | Day 730 Post-Transplant |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cyclophosphamide and Bortezomib | Bortezomib: 1.3 mg/m2 IV 6 hours after graft infusion and 72 hours thereafter. Cyclophosphamide: 50 mg/kg IV over 2 hours on Day +3 and +4 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 |
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| 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 | Percentage of Participants Who Experience Acute GvHD | Rate of acute GvHD post-transplant. All participants that received a transplant and received any prophylactic treatment will be included in the analysis. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 120 Post-Transplant |
|
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| ||||||||||||||||||||||||||
| Primary | Percentage of Participants Who Experience Moderate to Severe Chronic GvHD | Rate of chronic GvHD post-transplant. All participants that received a transplant and received any prophylactic treatment will be included in the analysis. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 365 Post-Transplant |
|
| |||||||||||||||||||||||||||
| Secondary | Incidence of Primary Graft Failure | Incidence of graft failure will be calculated from date of transplant to failure for all patients who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment. Graft failure is defined as failure to achieve neutrophil engraftment by day 28 post-transplant or lack of donor chimerism > 50% by day 45 post-transplant not due to the underlying malignancy. | Posted | Number | Percentage of participants | Day 45 Post-Transplant |
|
| ||||||||||||||||||||||||||||
| Secondary | Incidence of Poor Graft Function | Incidence of poor graft function will be calculated from date of transplant to failure for all patients who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment. Poor graft function is defined by at least 2 of the following 3 criteria: Hemoglobin < 8 g/dL, ANC < 0.5 109/L, and platelets < 20 109/L. The cytopenia must be unexplained (such as by disease relapse) and unresponsive to cytokines and must last at least 4 weeks. | Posted | Number | Percentage of participants | Day 30 Post-Transplant |
|
| ||||||||||||||||||||||||||||
| Secondary | Incidence of Secondary Graft Failure | Incidence of secondary graft failure is evaluated after engraftment is achieved; this outcome is calculated from date of engraftment for all patients with engraftment. Secondary graft failure is defined as poor graft function associated with donor chimerism < 5%. | Posted | Number | Percentage of participants | Day 730 Post-Transplant |
|
| ||||||||||||||||||||||||||||
| Secondary | Treatment Related Mortality (TRM) | Number of participant deaths not attributable to disease relapse or progression . This outcome is analyzed based on participants that who received a transplant with any prophylactic treatment and for all patients who received a transplant and completed prophylactic treatment. | Posted | Count of Participants | Participants | Day 730 Post-Transplant |
|
| ||||||||||||||||||||||||||||
| Secondary | Relapse Rate (RR) | Percentage of participants in whom the disease for which transplant is performed is evident by methods of disease detection after transplant. This outcome is analyzed for all patients who received a transplant and for all transplanted patients that completed treatment. | Posted | Number | Percentage of participants | Day 730 Post-Transplant |
|
| ||||||||||||||||||||||||||||
| Secondary | Graft Versus Host Disease Relapse Free Survival (GRFS) | Percentage of participants who are without reported GvHD III-IV acute GvHD, chronic GvHD requiring systemic therapy and have not experienced relapse or death after transplant. | Posted | Number | Percentage of participants | Day 730 Post-Transplant |
|
| ||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | Percentage of participants alive at the end of the study's evaluation period. | Posted | Number | Percentage of participants | Day 730 Post-Transplant |
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Adverse events assessed from the start of the conditioning regimen for a minimum of 30 days after the last treatment dose (41 days total). All-cause mortality assessed through day 730 Post-Transplant.
Investigator assessment at each study visit.
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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 | Cyclophosphamide and Bortezomib | Bortezomib: 1.3 mg/m2 IV 6 hours after graft infusion and 72 hours thereafter. Cyclophosphamide: 50 mg/kg IV over 2 hours on Day +3 and +4 | 2 | 16 | 7 | 16 | 10 | 16 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | Systematic Assessment |
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| Blood Bilirubin Increased | Investigations | Systematic Assessment |
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| Confusion | Psychiatric disorders | Systematic Assessment |
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| Cytomegalovirus Infection Reactivation | Infections and infestations | Systematic Assessment |
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| Death | General disorders | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Fever | General disorders | Systematic Assessment |
| ||
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypotension | Vascular disorders | Systematic Assessment |
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| COVID Infection | Infections and infestations | Systematic Assessment |
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| BK Viremia | Infections and infestations | Systematic Assessment |
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| Adenovirus | Infections and infestations | Systematic Assessment |
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| Methemoglobinemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Syncope | Nervous system disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Agitation | Psychiatric disorders | Systematic Assessment |
| ||
| Alanine Aminotransferase Increased | Investigations | Systematic Assessment |
| ||
| Alkaline Phosphatase Increased | Investigations | Systematic Assessment |
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| Aspartate Aminotransferase Increased | Investigations | Systematic Assessment |
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| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
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| Bacteremia | Infections and infestations | Systematic Assessment |
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| Bloating | Gastrointestinal disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Epstein-Barr virus infection reactivation | Infections and infestations | Systematic Assessment |
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| Febrile Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Gastric Hemorrhage | Gastrointestinal disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Hematuria | Renal and urinary disorders | Systematic Assessment |
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| Hypertension | Vascular disorders | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypoxia | Infections and infestations | Systematic Assessment |
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| C. Difficile | Infections and infestations | Systematic Assessment |
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| Mucositis Oral | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Pain | General disorders | Systematic Assessment |
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| Platelet Count Decreased | Investigations | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Secretions | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Sinus Tachycardia | Cardiac disorders | Systematic Assessment |
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| Skin Ulceration | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Sore Throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Upper Gastrointestinal Hemorrhage | Gastrointestinal disorders | Systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | Systematic Assessment |
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| Viremia | Infections and infestations | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ahmad Al-Homsi | NYU Langone Health | 6465017621 | Samer.Al-Homsi@nyulangone.org |
| Oct 19, 2023 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000069286 | Bortezomib |
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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