This is a phase I-II clinical trial. Adult subjects with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated donor are eligible for the study if they meet the criteria defined in our standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Subjects will receive a standard of care conditioning regimen. Subjects will receive investigational PTCy, investigational bortezomib and investigational abatacept as GvHD prophylaxis.
The study will have a phase I and phase II potions. The phase I portion will employ a 3+3 dose escalation design to define the maximum tolerated dose (MTD) of abatacept added to PTCy and bortezomib following HSCT. The phase II portion will consist of two single arm, open label, optimal 2-stage Simon design studies conducted in two separate strata for HLA matched and HLA mismatched donor transplants. Adult patients with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated 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. Subjects will receive a standard of care conditioning regimen followed by peripheral blood hematopoietic stem cells. Subjects with unrelated donors will also receive rabbit anti-thymocyte globulin (rATG). Subjects will receive investigational PTCy, investigational bortezomib and investigational abatacept as GvHD prophylaxis. The phase II portion dose of abatacept will be the MTD as determined in the phase I portion of the study. In the phase II portions, subjects will be stratified based on whether they receive a matched sibling or matched unrelated (matched) donor transplant and ≥7 out of 8, allele level matched (mismatched) unrelated donor transplant.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
74
37.5 mg/kg IV over 1 hour on Day +3 and +4
Dose level 0: 10 mg/kg IV over 30-60 minutes on day +5 Dose level 1: 10mg/kg IV over 30-60 minutes on day +5 and +14 Dose level 2: 10mg/kg IV over 30-60 minutes on day +5, +14, and +28
1.3 mg/m2 IV 6 hours after graft infusion completion and 72 hours thereafter.
Northwell Health
New Hyde Park, New York, United States
RECRUITINGPhase I:Incidence Dose limiting toxicity (DLT)
Defined as grade 4 non-hematologic toxicity affecting the oral cavity, gastrointestinal tract, lung, heart, liver, kidney, bladder, or central nervous system.
Time frame: Day+1 to Day +120
Phase II: Grades II-IV Acute GvHD
The first day of grades II-IV acute GvHD will be recorded for that grade. This end point will be evaluated through day +120 post-transplant.
Time frame: Day+1 to Day +120
Chronic GvHD
The diagnosis of chronic GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.The analysis will be based on the maximum grade of chronic GvHD
Time frame: Day +1 to Day +365
Primary graft failure
Incidence of graft failure will be calculated from date of transplant to failure for all subjects who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment
Time frame: Day +1 to Day +30
Poor graft function
Incidence of poor graft function will be calculated, from date of transplant to failure for all subjects who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment
Time frame: Day +1 to Day +30
Secondary graft failure
Evaluated after engraftment is achieved will be calculated from date of engraftment for all subjects with engraftment
Time frame: Day +1
Treatment-related mortality (TRM)
Analyzed based on participants that who received a transplant with any prophylactic treatment and for all subjects who received a transplant and completed prophylactic treatment.
Time frame: Day +1 to Day +730
Relapse rate (RR)
Evaluated to day +730 and will be analyzed for all subjects who received a transplant and for all transplanted subjects that completed treatment
Time frame: Day +1 to Day +730
GvHD and relapse-free survival (GRFS)
Evaluated to day +730 and considers as successes participants that are without reported GvHD III-IV acute GvHD, chronic GvHD requiring systemic therapy and have not experienced relapse or death after transplant
Time frame: Day +1 to Day +730
Overall survival (OS)
Evaluated to day +730 and considers all participants who received a transplant and for all transplanted subjects who completed prophylactic treatment
Time frame: Day +1 to Day +730
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