Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention

NCT ID: NCT04503616

Last Updated: 2024-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-16
• Study Completion Date: 2024-08-15

Brief Summary

This is a single arm, open label, optimal 2-stage Simon design phase Ib-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 cyclophosphamide, abatacept, and short-duration tacrolimus for GvHD prophylaxis.

Conditions

Graft-versus-host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

HSCT Patients

Adult patients with hematological malignancies undergoing HLA-haploidentical HSCT from first-or second-degree family donors.

Group Type: EXPERIMENTAL

Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention

Intervention Type: DRUG

Cyclophosphamide 50 mg/kg IV over 2 hours on Day +3 and +4 Abatacept 10 mg/kg IV on days +5, +14, and +28 Tacrolimus 0.02 mg/kg IV by continuous infusion, starting on day +5. May switch to oral when tolerated, adjusted to maintain a drug level between 5-12ng/mL. Treatment is discontinued on day +60 after a 4 week-taper

Interventions

Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention

Cyclophosphamide 50 mg/kg IV over 2 hours on Day +3 and +4 Abatacept 10 mg/kg IV on days +5, +14, and +28 Tacrolimus 0.02 mg/kg IV by continuous infusion, starting on day +5. May switch to oral when tolerated, adjusted to maintain a drug level between 5-12ng/mL. Treatment is discontinued on day +60 after a 4 week-taper

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. Karnofsky score ≥ 70%

3. No evidence of progressive bacterial, viral, or fungal infection

4. Creatinine clearance > 50 mL/min/1.72m2

5. Total bilirubin, ALT and AST < 2 x the upper limit of normal (except for diagnosed Gilbert's syndrome)

6. Alkaline phosphatase ≤ 250 IU/L

7. Left Ventricular Ejection Fraction (LVEF) > 45%

8. Adjusted Carbon Monoxide Diffusing Capacity (DLCO) > 60%

9. Negative HIV serology

10. Negative pregnancy test: confirmation per negative serum β-human chorionic gonadotropin (β-hCG) for women of childbearing age and potential.

Exclusion Criteria

1. Donors are excluded in case of donor-specific HLA antibodies or positive cross-match.

2. 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.

3. 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).

4. Inability to provide informed consent.

5. 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.

6. Known allergies to any of the components of the investigational treatment regimen.

7. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

8. 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.

9. Prisoners

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maher Abdul Hay, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

NYU Langone Health

New York, New York, United States

Countries

United States

References

Al-Homsi AS, Cirrone F, Wo S, Cole K, Suarez-Londono JA, Gardner SL, Hsu J, Stocker K, Bruno B, Goldberg JD, Levinson BA, Abdul-Hay M. PTCy, abatacept, and a short course of tacrolimus for GVHD prevention after haploidentical transplantation. Blood Adv. 2023 Jul 25;7(14):3604-3611. doi: 10.1182/bloodadvances.2023010545.

Reference Type: DERIVED

PMID: 37163349 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

20-00136

Identifier Type: -

Identifier Source: org_study_id