Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention

NCT04503616 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 20-00136
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Grade II-IV Acute GvHD by Day +120

  The first day of grade II-IV acute GvHD will be used to calculate the cumulative incidence. The cumulative incidence will be defined as the percentage of participants with grade II-IV acute GvHD. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician. Overall Grades of Acute GvHD: 0 = none; 1. = mild; 2. = moderate; 3. = severe; 4. = life threatening

  120 days

Secondary Outcomes (8)

• Cumulative Incidence of Chronic GvHD

  Day 365

• Cumulative Incidence of Primary Graft Failure

  Day 45

• Cumulative Incidence of Poor Graft Function

  Day 28

• Incidence of Secondary Graft Failure

  Day 730

• Number of Treatment-Related Deaths

  Day 730

Study Arms (1)

HSCT Patients

EXPERIMENTAL

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

Drug: Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention

Interventions

Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention 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

HSCT Patients

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
• Total bilirubin, ALT and AST \< 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

Related Publications (1)

• 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.

  PMID: 37163349 DERIVED

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

Results Point of Contact

• Title: Kelli Cole, NP
• Organization: NYU Langone Health

Kelli.Cole@NYULangone.org

646-501-4848

Study Officials

• Maher Abdul Hay, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: Interventional, non-randomized open label, 2- stage optimal Simon design with interim futility analysis.

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 7, 2020
• Study Start: September 16, 2020
• Primary Completion: December 14, 2022
• Study Completion: August 15, 2024
• Last Updated: October 16, 2024
• Results First Posted: November 8, 2023

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: beginning 9 months and ending 36 months following article publication
• Access Criteria: The investigator who proposed to use the data will be provided access upon reasonable request. Requests should be directed to Maher.Abdulhay@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)