Post-Transplant Cyclophosphamide, Bortezomib and Abatacept for the Prevention of Graft-versus-Host-Disease (GvHD)

NCT05289167 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 21-00797
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Graft-versus-host Disease

Keywords

GvHD, post transplant cyclophosphamide, abatacept

Outcome Measures

Primary Outcomes (2)

• Phase I:Incidence Dose limiting toxicity (DLT)

  Defined as grade 4 non-hematologic toxicity affecting the oral cavity, gastrointestinal tract, lung, heart, liver, kidney, bladder, or central nervous system.

  Day+1 to Day +120

• Phase II: Grades II-IV Acute GvHD

  The first day of grades II-IV acute GvHD will be recorded for that grade. This end point will be evaluated through day +120 post-transplant.

  Day+1 to Day +120

Secondary Outcomes (8)

• Chronic GvHD

  Day +1 to Day +365

• Primary graft failure

  Day +1 to Day +30

• Poor graft function

  Day +1 to Day +30

• Secondary graft failure

  Day +1

• Treatment-related mortality (TRM)

  Day +1 to Day +730

Study Arms (1)

Participants with hematological malignancies

EXPERIMENTAL

Participants undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) will receive a combination of cyclophosphamide, known commercially as Cytoxan®, abatacept, known as Orecia® and bortezomib commercially known as Velcade®, to reduce the rate of graft-versus-host disease (GvHD). These medications will be given for GvHD prevention during the transplant process.

Drug: Cyclophosphamide; Drug: Abatacept; Drug: Bortezomib

Interventions

Cyclophosphamide DRUG

50 mg/kg IV over 1 hour on Day +3 and +4

Also known as: Cytoxan®

Participants with hematological malignancies

Abatacept DRUG

Dose level 0: 10 mg/kg IV over 30 minutes on day +5 Dose level 1: 10mg/kg IV over 30 minutes on day +5 and +14 Dose level 2: 10mg/kg IV over 30 minutes on day +5, +14, and +28

Also known as: Orecia®

Participants with hematological malignancies

Bortezomib DRUG

1.3 mg/m2 IV 6 hours after graft infusion completion and 72 hours thereafter.

Also known as: Velcade®

Participants with hematological malignancies

Eligibility Criteria

• Age: 18 Years - 100 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)
• 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.

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 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Northwell Health

New Hyde Park, New York, 10016, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Cyclophosphamide; Abatacept; Bortezomib

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• A. Samer Al-Homsi, MD, MBA

  Northwell Health

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 10, 2022
• First Posted: March 21, 2022
• Study Start: March 13, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)