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

Launched by NORTHWELL HEALTH · Nov 7, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach to help prevent Graft-Versus-Host Disease (GVHD) in patients who have received a stem cell transplant. GVHD is a condition where the donated stem cells attack the recipient's body, which can lead to serious complications. The trial will investigate a combination of three medications—high-dose post-transplant cyclophosphamide, bortezomib, and abatacept—to see how well they work together and to find the safest doses for patients. The study is conducted in two phases, with the first phase focusing on determining the highest dose that can be tolerated without severe side effects.

To be eligible for this trial, participants must be at least 18 years old, in good overall health, and not currently battling any severe infections. They should have good kidney function and meet other health criteria, such as having a certain level of heart and lung function. Participants can expect to undergo regular health assessments and will need to comply with the study procedures for the duration of the trial. Importantly, women who can become pregnant and men must agree to use contraception during the study to avoid any potential risks. Overall, this trial aims to improve outcomes for patients undergoing stem cell transplants by preventing GVHD, which is a significant concern in this treatment process.

Gender

ALL

Eligibility 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)
• • ALP ≤250 IU/L
• • LVEF \>45%
• • Adjusted DLCO \>50%
• • Negative HIV serology
• • Negative pregnancy test: Confirmation per negative serum 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 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 consecutive months.
• • 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.
• • Inability to provide informed consent.
• • Patient had myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, 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 is 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