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AzTrials

Graft-versus-host DiseasePhase 1/2NCT04503616

Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention

A Phase 1/2 study testing Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention in people with Graft-versus-host Disease, run by NYU Langone Health at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft-versus-host Disease
What is being tested?
Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
1 siteUnited States
Study dates
16 Sep 2020to 15 Aug 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • NYU Langone Health

    New York, New York, 10016

Other trials in United States

About this study

Official title: A Phase IB-II Study Of High-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration Tacrolimus for the Prevention of Graft-Versus-Host Disease (GvHD) Following Haploidentical Hematopoietic Stem Cell Transplantation (HSCT)

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.

Being tested
Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention
Medical subject headings
Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cyclophosphamide, Abatacept, and Tacrolimus for GvHD PreventionDrug

    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

Study groups in NCT04503616
Study groupRoleWhat they receive
HSCT PatientsExperimentalAdult patients with hematological malignancies undergoing HLA-haploidentical HSCT from first-or second-degree family donors.
Receives: Drug: Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 120 days

Secondary outcomes (8)

  1. Cumulative Incidence of Chronic GvHD

    The first day of chronic GvHD will be used to calculate the cumulative incidence of chronic GvHD. This endpoint will be evaluated through day +365 post-transplant.

    Measured: Day 365

  2. Cumulative Incidence of Primary Graft Failure

    Graft failure is defined as failure to achieve neutrophil engraftment by day +28 or lack of donor chimerism > 50% by day 45, not due to the underlying malignancy.

    Measured: Day 45

  3. Cumulative Incidence of Poor Graft Function

    Poor Graft Function defined by at least 2 of the following 3 criteria: Hemoglobin < 8 g/dL, ANC < 0.5 x 109/L, and platelets < 20 x 109/L. The cytopenia must be unexplained (such as by disease relapse) and unresponsive to cytokines and must last at least 4 weeks.

    Measured: Day 28

  4. Incidence of Secondary Graft Failure

    Evaluated following engraftment through day +730. Secondary Graft Failure defined as poor graft function associated with donor chimerism < 5%.

    Measured: Day 730

  5. Number of Treatment-Related Deaths

    Number of participant deaths not attributable to disease relapse or progression. Will be evaluated to day +730.

    Measured: Day 730

  6. Relapse Rate

    Evaluated to day +730 and defined as the percentage of patients in whom the disease for which transplant is performed becomes evident by methods of disease detection after the transplant.

    Measured: Day 730

  7. GvHD and Relapse-Free Survival (GRFS)

    Evaluated to day +730 and defined as the percentage of participants who are without reported grade III-IV acute GvHD, without chronic GvHD requiring systemic therapy, and have not experienced relapse or death.

    Measured: Day 730

  8. Overall Survival

    Evaluated to day +730 and defined as percentage of participants alive at the end of the study's evaluation period.

    Measured: Day 730

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2020
  2. Study start16 Sep 2020
  3. Primary completion14 Dec 2022
  4. Study completion15 Aug 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Model description
Interventional, non-randomized open label, 2- stage optimal Simon design with interim futility analysis.
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04503616
Sponsor's protocol ID
20-00136
Status last verified
Oct 2024
First submitted
5 Aug 2020
Last updated
16 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Maher.Abdulhay@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Publications

  • 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.

    PubMed 37163349

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention in people with Graft-versus-host Disease, run by NYU Langone Health at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Grade II-IV Acute GvHD by Day +120 (time frame: 120 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04503616, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2024.

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