High-Dose Post-Transplant Cyclophosphamide and Bortezomib (CyBor) for the Prevention of Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cyclophosphamide and Bortezomib
|
Drug: Bortezomib
1.3 mg/m2 IV 6 hours after graft infusion and 72 hours thereafter.
Drug: Cyclophosphamide
50 mg/kg IV over 2 hours on Day +3 and +4
|
Outcome Measures
Primary Outcome Measures
- Incidence of Acute GvHD [Day +45]
The first day of acute GvHD of any grade will be recorded for that grade. This end point will be evaluated through day +120 post-transplant. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician. Cumulative incidence curves will be provided along with 95% confidence intervals for the 120 day cumulative incidence.
- Incidence of Chronic GvHD [Day +45]
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
- Primary graft failure [Day +45]
evaluated to day +45 and 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.
- Poor graft function [Day +30]
evaluated to day +30 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.
- Secondary graft failure [day +730]
evaluated after engraftment is achieved will be calculated from date of engraftment for all patients with engraftment.
- Treatment Related Mortality (TRM) [day +730]
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) [day +730]
analyzed for all patients who received a transplant and for all transplanted patients that completed treatment.
- Graft versus Host Disease Relapse Free Survival (GRFS) [day +730]
participants that 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) [day +730]
considers all participants who received a transplant and for all transplanted patients who completed prophylactic treatment as described above. .
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Karnofsky score ≥ 70%
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No evidence of progressive bacterial, viral, or fungal infection
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Creatinine clearance > 50 mL/min/1.72m2
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Total bilirubin, ALT and AST < 2 x the upper limit of normal (except for Gilbert's syndrome)
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Alkaline phosphatase ≤ 250 IU/L
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Left Ventricular Ejection Fraction (LVEF) > 45%
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Adjusted Carbon Monoxide Diffusing Capacity (DLCO) > 60%
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Negative HIV serology
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Negative pregnancy test: confirmation per negative serum β-human chorionic gonadotropin (β-hCG)
Exclusion Criteria:
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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.
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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).
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Inability to provide informed consent.
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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.
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Known allergies to any of the components of the investigational treatment regimen.
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Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
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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.
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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.
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Prisoners
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New York University School of Medicine | New York | New York | United States | 10016 |
Sponsors and Collaborators
- NYU Langone Health
Investigators
- Principal Investigator: Ahmad Al-Homsi, MD, New York Langone Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 18-01185