Preventing Graft-Versus-Host Disease After Stem Cell Transplant

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)

This study is testing whether a combination of three medications can help prevent graft-versus-host disease in adults with blood cancers who are getting a stem cell transplant.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Northwell Health (other)
• Locations: 1 site (Lake Success, New York)
• Trial ID: NCT06681922 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of high-dose post-transplant cyclophosphamide, bortezomib, and abatacept in preventing graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). It consists of two phases: the first phase will determine the maximum tolerated dose of abatacept, while the second phase will assess the treatment's efficacy in two groups based on donor matching. Participants will receive standard conditioning regimens followed by the investigational drugs as GVHD prophylaxis. The study will include adult patients with hematological malignancies and will be conducted at the Zuckerberg Cancer Center in New York.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with hematological malignancies who are undergoing allogeneic HSCT from HLA-matched or mismatched donors.

Not a fit: Patients who are pregnant, nursing, or have certain medical conditions that do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the incidence of GVHD in patients undergoing stem cell transplants.

How similar studies have performed: Other studies have explored similar approaches to GVHD prevention, but this specific combination of treatments is novel.

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

Where this trial is running

Lake Success, New York

• Zuckerberg Cancer Center — Lake Success, New York, United States (RECRUITING)

Study contacts

• Study coordinator: Kelli Cole

Conditions: Graft Vs Host Disease