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)

NCT06681922 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 24-0599
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The study will be conducted in two phases. The phase I portion will employ a 3+3 dose-escalation design to define the maximum tolerated dose (MTD) of abatacept added to PTCy and bortezomib following HSCT. The phase II portion will consist of two single-arm, open-label, optimal 2-stage Simon design studies conducted in two separate strata for HLA-matched and HLA-mismatched donor transplants.

Conditions

Graft Vs Host Disease

Outcome Measures

Primary Outcomes (1)

• Determine the MTD of abatacept in combination with PTCy and bortezomib Determine the MTD of abatacept in combination with PTCy and bortezomib Determine the MTD of abatacept in combination with PTCy and bortezomib

  Up to 2 years

Interventions

Cyclophosphamide, Bortezomib, Abatacept DRUG

Drug given for prevention of Graft-versus-Host Disease (GvHD) following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Zuckerberg Cancer Center

Lake Success, New York, 11042, United States

RECRUITING

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Cyclophosphamide; Bortezomib; Abatacept

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Central Study Contacts

Kelli Cole

CONTACT

5167348900; kcole5@northwell.edu

Ahmad Samer Al-Homsi, MD

CONTACT

5165622945; asameralhomsi@northwell.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2024
• First Posted: November 12, 2024
• Study Start: September 23, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 16, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)