Back to resultsHigh-Dose Post-Transplant Cyclophosphamide and Bortezomib (CyBor) for the Prevention of Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Primary Purpose
GVHD
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bortezomib
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for GVHD focused on measuring Cyclophosphamide, Bortezomib
Eligibility Criteria
Inclusion Criteria:
- Karnofsky score ≥ 70%
- No evidence of progressive bacterial, viral, or fungal infection
- Creatinine clearance > 50 mL/min/1.72m2
- Total bilirubin, ALT and AST < 2 x the upper limit of normal (except for Gilbert's syndrome)
- Alkaline phosphatase ≤ 250 IU/L
- Left Ventricular Ejection Fraction (LVEF) > 45%
- Adjusted Carbon Monoxide Diffusing Capacity (DLCO) > 60%
- Negative HIV serology
- Negative pregnancy test: confirmation per negative serum β-human chorionic gonadotropin (β-hCG)
Exclusion Criteria:
- Pregnant or nursing females or women of reproductive capability who are unwilling to completely abstain from heterosexual sex or practice 2 effective methods of contraception from the first dose of bortezomib through 90 days after the last dose. A woman of reproductive capability is one who has not undergone a hysterectomy (removal of the womb), has not had both ovaries removed, or has not been post-menopausal (stopped menstrual periods) for more than 24 months in a row.
- Male subjects who refuse to practice effective barrier contraception during the entire study treatment period and through a minimum of 90 days after the last dose of study drug, or completely abstain from heterosexual intercourse. This must be done even if they are surgically sterilized (i.e., post-vasectomy).
- Inability to provide informed consent.
- Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see Appendix E), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
- Known allergies to any of the components of the investigational treatment regimen.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma, an in-situ malignancy, or low-risk prostate cancer after curative therapy.
- Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
- Prisoners
Sites / Locations
- New York University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cyclophosphamide and Bortezomib
Arm Description
Outcomes
Primary Outcome Measures
Incidence of Acute GvHD
The first day of acute GvHD of any grade will be recorded for that grade. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.
Incidence of Chronic GvHD
The first day of chronic GvHD will be recorded. The diagnosis of chronic GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician. All participants that completed transplant and any prophylactic treatment will be included in the analysis.
Secondary Outcome Measures
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.
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.
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%.
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.
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.
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.
Overall Survival (OS)
Percentage of participants alive at the end of the study's evaluation period.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03945591
Brief Title
High-Dose Post-Transplant Cyclophosphamide and Bortezomib (CyBor) for the Prevention of Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Official Title
A Phase II Study of High-Dose Post-Transplant Cyclophosphamide and Bortezomib (CyBor) for the Prevention of Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 20, 2019 (Actual)
Primary Completion Date
December 29, 2022 (Actual)
Study Completion Date
January 4, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
GVHD
Keywords
Cyclophosphamide, Bortezomib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cyclophosphamide and Bortezomib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Intervention Description
1.3 mg/m2 IV 6 hours after graft infusion and 72 hours thereafter.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
50 mg/kg IV over 2 hours on Day +3 and +4
Primary Outcome Measure Information:
Title
Incidence of Acute GvHD
Description
The first day of acute GvHD of any grade will be recorded for that grade. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.
Time Frame
Day 120 Post-Transplant
Title
Incidence of Chronic GvHD
Description
The first day of chronic GvHD will be recorded. The diagnosis of chronic GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician. All participants that completed transplant and any prophylactic treatment will be included in the analysis.
Time Frame
Day 365 Post-Transplant
Secondary Outcome Measure Information:
Title
Incidence of Primary Graft Failure
Description
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.
Time Frame
Day 45 Post-Transplant
Title
Incidence of Poor Graft Function
Description
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.
Time Frame
Day 30 Post-Transplant
Title
Incidence of Secondary Graft Failure
Description
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%.
Time Frame
Day 730 Post-Transplant
Title
Treatment Related Mortality (TRM)
Description
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.
Time Frame
Day 730 Post-Transplant
Title
Relapse Rate (RR)
Description
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.
Time Frame
Day 730 Post-Transplant
Title
Graft versus Host Disease Relapse Free Survival (GRFS)
Description
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.
Time Frame
Day 730 Post-Transplant
Title
Overall Survival (OS)
Description
Percentage of participants alive at the end of the study's evaluation period.
Time Frame
Day 730 Post-Transplant
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Karnofsky score ≥ 70%
No evidence of progressive bacterial, viral, or fungal infection
Creatinine clearance > 50 mL/min/1.72m2
Total bilirubin, ALT and AST < 2 x the upper limit of normal (except for Gilbert's syndrome)
Alkaline phosphatase ≤ 250 IU/L
Left Ventricular Ejection Fraction (LVEF) > 45%
Adjusted Carbon Monoxide Diffusing Capacity (DLCO) > 60%
Negative HIV serology
Negative pregnancy test: confirmation per negative serum β-human chorionic gonadotropin (β-hCG)
Exclusion Criteria:
Pregnant or nursing females or women of reproductive capability who are unwilling to completely abstain from heterosexual sex or practice 2 effective methods of contraception from the first dose of bortezomib through 90 days after the last dose. A woman of reproductive capability is one who has not undergone a hysterectomy (removal of the womb), has not had both ovaries removed, or has not been post-menopausal (stopped menstrual periods) for more than 24 months in a row.
Male subjects who refuse to practice effective barrier contraception during the entire study treatment period and through a minimum of 90 days after the last dose of study drug, or completely abstain from heterosexual intercourse. This must be done even if they are surgically sterilized (i.e., post-vasectomy).
Inability to provide informed consent.
Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see Appendix E), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
Known allergies to any of the components of the investigational treatment regimen.
Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma, an in-situ malignancy, or low-risk prostate cancer after curative therapy.
Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
Prisoners
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ahmad Al-Homsi, MD
Organizational Affiliation
New York Langone Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York University School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
IPD Sharing Access Criteria
Requests should be directed to Ankeeta.Joshi@nyulangone.org To gain access, data requestors will need to sign a data access agreement.
Learn more about this trial
High-Dose Post-Transplant Cyclophosphamide and Bortezomib (CyBor) for the Prevention of Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
We'll reach out to this number within 24 hrs