Overview

A Phase I-II Study of High-Dose Post-Transplant Cyclophosphamide, Bortezomib and Abatacept for the Prevention of Graft-versus-Host-Disease (GvHD) Following Allogenic Hematopoietic Stem Cell Transplantation (HSCT)

Status:
Not yet recruiting
Trial end date:
2024-03-01
Target enrollment:
0
Participant gender:
All
Summary
This is a phase I-II clinical trial. Adult subjects with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated donor are eligible for the study if they meet the criteria defined in our standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Subjects will receive a standard of care conditioning regimen. Subjects will receive investigational PTCy, investigational bortezomib and investigational abatacept as GvHD prophylaxis.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
NYU Langone Health
Treatments:
Abatacept
Bortezomib
Cyclophosphamide
Criteria
Inclusion Criteria:

- Age ≥18 years

- Karnofsky score ≥70%

- No evidence of progressive bacterial, viral, or fungal infection

- Creatinine clearance >50 mL/min/1.72m2

- ALT and AST <3 x the upper limit of normal

- Total bilirubin <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) >50%

- Negative HIV serology

- Negative pregnancy test: Confirmation per negative serum β-human chorionic
gonadotropin (β-hCG)

- Willing to comply with all study procedures and be available for the duration of the
study.

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 start of conditioning through 90 days after the last dose of study
drug. 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 from the start of
conditioning 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 D), 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

- Pregnant women