Clinical trial NCT03945591: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: GVHD
Keywords: Cyclophosphamide
Bortezomib
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2019-05-10
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants Who Experience Acute GvHD
timeFrame: Day 120 Post-Transplant
measure: Percentage of Participants Who Experience Moderate to Severe Chronic GvHD
timeFrame: Day 365 Post-Transplant
Secondary outcomes:
measure: Incidence of Primary Graft Failure
timeFrame: Day 45 Post-Transplant
measure: Incidence of Poor Graft Function
timeFrame: Day 30 Post-Transplant
measure: Incidence of Secondary Graft Failure
timeFrame: Day 730 Post-Transplant
measure: Treatment Related Mortality (TRM)
timeFrame: Day 730 Post-Transplant
measure: Relapse Rate (RR)
timeFrame: Day 730 Post-Transplant
measure: Graft Versus Host Disease Relapse Free Survival (GRFS)
timeFrame: Day 730 Post-Transplant
measure: Overall Survival (OS)
timeFrame: Day 730 Post-Transplant
Other outcomes:
Locations:
city: New York
country: United States
facility: New York University School of Medicine
state: New York
Study officials:
affiliation: New York Langone Medical Center
name: Ahmad Al-Homsi, MD
role: PRINCIPAL_INVESTIGATOR
References: