Back to resultsCyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention
Primary Purpose
Graft-versus-host Disease
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention
Sponsored by
About this trial
This is an interventional prevention trial for Graft-versus-host Disease
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- NYU Langone Health
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
HSCT Patients
Arm Description
Adult patients with hematological malignancies undergoing HLA-haploidentical HSCT from first-or second-degree family donors.
Outcomes
Primary Outcome Measures
Cumulative Incidence of 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 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;
= mild;
= moderate;
= severe;
= life threatening
Secondary Outcome Measures
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.
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.
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.
Incidence of Secondary Graft Failure
Evaluated following engraftment through day +730. Secondary Graft Failure defined as poor graft function associated with donor chimerism < 5%.
Number of Treatment-Related Deaths
Number of participant deaths not attributable to disease relapse or progression. Will be evaluated to day +730.
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.
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.
Overall Survival
Evaluated to day +730 and defined as percentage of participants alive at the end of the study's evaluation period.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04503616
Brief Title
Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention
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)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 16, 2020 (Actual)
Primary Completion Date
December 14, 2022 (Actual)
Study Completion Date
June 20, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft-versus-host Disease
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Interventional, non-randomized open label, 2- stage optimal Simon design with interim futility analysis.
Masking
None (Open Label)
Allocation
N/A
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HSCT Patients
Arm Type
Experimental
Arm Description
Adult patients with hematological malignancies undergoing HLA-haploidentical HSCT from first-or second-degree family donors.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention
Intervention Description
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
Primary Outcome Measure Information:
Title
Cumulative Incidence of Grade II-IV Acute GvHD by Day +120
Description
The first day of grade II-IV acute GvHD will be used to calculate the cumulative incidence. 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;
= mild;
= moderate;
= severe;
= life threatening
Time Frame
120 days
Secondary Outcome Measure Information:
Title
Cumulative Incidence of Chronic GvHD
Description
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.
Time Frame
Day 365
Title
Cumulative Incidence of Primary Graft Failure
Description
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.
Time Frame
Day 45
Title
Cumulative Incidence of Poor Graft Function
Description
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.
Time Frame
Day 28
Title
Incidence of Secondary Graft Failure
Description
Evaluated following engraftment through day +730. Secondary Graft Failure defined as poor graft function associated with donor chimerism < 5%.
Time Frame
Day 730
Title
Number of Treatment-Related Deaths
Description
Number of participant deaths not attributable to disease relapse or progression. Will be evaluated to day +730.
Time Frame
Day 730
Title
Relapse Rate
Description
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.
Time Frame
Day 730
Title
GvHD and Relapse-Free Survival (GRFS)
Description
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.
Time Frame
Day 730
Title
Overall Survival
Description
Evaluated to day +730 and defined as percentage of participants alive at the end of the study's evaluation period.
Time Frame
Day 730
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samer Al-Homsi, MD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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 the PI. 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.
IPD Sharing Time Frame
beginning 9 months and ending 36 months following article publication
IPD Sharing Access Criteria
Requests may be directed to the PI.
Learn more about this trial
Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention
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