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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
46
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
NYU Langone Health
New York, New York, United States
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
Time frame: 120 days
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.
Time frame: Day 365
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.
Time frame: Day 45
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.
Time frame: Day 28
Incidence of Secondary Graft Failure
Evaluated following engraftment through day +730. Secondary Graft Failure defined as poor graft function associated with donor chimerism \< 5%.
Time frame: Day 730
Number of Treatment-Related Deaths
Number of participant deaths not attributable to disease relapse or progression. Will be evaluated to day +730.
Time frame: 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.
Time frame: Day 730
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.
Time frame: Day 730
Overall Survival
Evaluated to day +730 and defined as percentage of participants alive at the end of the study's evaluation period.
Time frame: Day 730
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