Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HSCT Patients Adult patients with hematological malignancies undergoing HLA-haploidentical HSCT from first-or second-degree family donors. |
Drug: 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
|
Outcome Measures
Primary Outcome Measures
- Incidence of Grade II-IV acute GvHD by day +120 [120 days]
The first day of acute GvHD of any grade will be used to calculate the cumulative incidence for that grade (e.g., onset of grade III 70 days post-transplant - time to grade III is 70 days). This end point will be evaluated through day +120 post-transplant. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician. Overall Grade acute GvHD: 0 none mild moderate severe life threatening
Secondary Outcome Measures
- Incidence of Chronic GvHD [365 Days]
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. Based on the organ scoring the severity of cGVHD is defined as follows: Mild cGVHD: involvement of 1-2 organs with maximum scores of 1 in all affected organs or sites. Moderate cGVHD: 1. involvement of 1-2 organ involvement with a maximum score of 2 in any affected organ or site (except for lungs). 2. involvement of 3 or more organs with maximum score of 1 in all affected organs or sites. Severe cGVHD: a lung score of 2 or a score 3 in any organ or site.
- Incidence of Primary graft failure [45 Days]
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.
- Incidence of Poor graft function [28 Days]
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 [730 Days]
Evaluated following engraftment through day +730. Defined as poor graft function associated with donor chimerism < 5%.
- Treatment-related mortality [730 Days]
Participant deaths not attributable to disease relapse or progression and will be evaluated to day +730.
- Relapse rate [730 Days]
evaluated to day +730 and is considered the date in which the disease for which transplant is performed is evident by methods of disease detection.
- GvHD and relapse-free survival [730 Days]
evaluated to day +730 and considers the number of participants that are without reported grade III-IV acute GvHD, chronic GvHD requiring systemic therapy and have not experienced relapse or death.
- Overall survival. [730 Days]
evaluated to day +730 and considers all participants alive at the end of the study's evaluation period.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 years
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Karnofsky score ≥ 70%
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No evidence of progressive bacterial, viral, or fungal infection
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Creatinine clearance > 50 mL/min/1.72m2
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Total bilirubin, ALT and AST < 2 x the upper limit of normal (except for diagnosed Gilbert's syndrome)
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Alkaline phosphatase ≤ 250 IU/L
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Left Ventricular Ejection Fraction (LVEF) > 45%
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Adjusted Carbon Monoxide Diffusing Capacity (DLCO) > 60%
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Negative HIV serology
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Negative pregnancy test: confirmation per negative serum β-human chorionic gonadotropin (β-hCG) for women of childbearing age and potential.
Exclusion Criteria:
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Donors are excluded in case of donor-specific HLA antibodies or positive cross-match.
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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.
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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).
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Inability to provide informed consent.
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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.
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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.
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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.
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Prisoners
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | NYU Langone Health | New York | New York | United States | 10016 |
Sponsors and Collaborators
- NYU Langone Health
Investigators
- Principal Investigator: Samer Al-Homsi, MD, NYU Langone Health
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20-00136