High-Dose Post-Transplant Cyclophosphamide and Bortezomib (CyBor) for the Prevention of Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Condition: GVHD
MeSH terms: Graft vs Host Disease
Intervention: Bortezomib; Cyclophosphamide
Intervention description: 1.3 mg/m2 IV 6 hours after graft infusion and 72 hours thereafter.; 50 mg/kg IV over 2 hours on Day +3 and +4
Intervention MeSH terms: Cyclophosphamide; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cyclophosphamide; Bortezomib

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