Cyclophosphamide, Abatacept, and Tacrolimus for the Prevention of GvHD

NCT05621759 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-00674
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, open label, phase II clinical trial. Adult patients with hematological malignancies undergoing allogeneic HSCT from first- or second-degree haploidentical donor are eligible for the study if they meet the standard criteria defined in our institutional standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Patients will receive non-myeloablative, reduced-intensity or myeloablative conditioning regimen followed by peripheral blood hematopoietic stem cells. Patients will receive dosed reduced cyclophosphamide, abatacept, and short-duration tacrolimus for GvHD prophylaxis.

Conditions

Graft Vs Host Disease

Keywords

Haploidentical Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Cumulative Incidence of Grades II-IV Acute GvHD

  The first day of acute GvHD of any grade is used to calculate the cumulative incidence for that grade. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.

  Up to Day 120

Secondary Outcomes (8)

• Cumulative Incidence of Chronic GvHD

  Up to Day 365

• Number of Participants Presenting with Primary Graft Failure

  Up to Day 45

• Number of Participants Presenting with Poor Graft Function

  Up to Day 30

• Number of Participants Presenting with Secondary Graft Failure

  Up to Day 730

• Treatment-Related Mortality (TRM) Rate

  Up to Day 730

Study Arms (1)

Reduced-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration Tacrolimus

EXPERIMENTAL

Participants to receive: * Cyclophosphamide 25 mg/kg IV over 1 hour on Day 3 and Day 4 following transplant * Abatacept 10 mg/kg IV on Day 5, Day 14, Day 28, and Day 56 following transplant * Tacrolimus 0.02 mg/kg IV by continuous infusion, starting on Day 5 following transplant. May switch to oral administration when tolerated, adjusted to maintain a drug level between 5-12ng/mL. Tacrolimus treatment is continued until Day 60 and then tapered over a period of 4 weeks in the absence of GvHD.

Drug: Cyclophosphamide; Drug: Abatacept; Drug: Tacrolimus

Interventions

Abatacept DRUG

Calcineurin-inhibitor produced by Astellas.

Also known as: Prograf

Reduced-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration Tacrolimus

Tacrolimus DRUG

Selective T cell co-stimulation modulator produced by Bristol-Myers Squibb.

Also known as: Orencia

Reduced-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration Tacrolimus

Cyclophosphamide DRUG

Nitrogen mustard alkylating agent produced by Bristol-Myers Squibb.

Also known as: Cytoxan

Reduced-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration Tacrolimus

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
• Total bilirubin, Alanine Aminotransferase and Aspartate Aminotransferase \< 2 x the upper limit of normal (except for diagnosed Gilbert's syndrome)
• Alkaline phosphatase ≤ 250 IU/L
• Left Ventricular Ejection Fraction (LVEF) \> 45%
• Adjusted Carbon Monoxide Diffusing Capacity (DLCO) \> 60%
• Negative HIV serology
• Negative pregnancy test: confirmation per negative serum β-human chorionic gonadotropin (β-hCG) for women of childbearing age and potential.

You may not qualify if:

• Donors are excluded in case of donor-specific HLA antibodies or positive cross-match.
• Pregnant or nursing females or women of child bearing age or potential, who are unwilling to completely abstain from heterosexual sex or practice 2 effective methods of contraception from the first dose of conditioning regimen through day +180. 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 during the entire study treatment period and 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 E), 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.
• 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

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Cyclophosphamide; Abatacept; Tacrolimus

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; Macrolides; Lactones

Study Officials

• Mohammad Maher Abdul Hay

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2022
• First Posted: November 18, 2022
• Study Start: September 7, 2022
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): January 30, 2027
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)