This is a prospective, multi-center, controlled, randomized, non-inferiority study to evaluate the clinical effectiveness of Conventional versus Mirasol-treated apheresis platelets in subjects with hypoproliferative thrombocytopenia who are expected to have platelet count(s) ≤ 10,000/μL requiring ≥ 2 platelet transfusions.
Patients will be randomized 1:1 to Mirasol-treated platelets (test platelets) or to conventional, untreated platelets (control platelets). The blood centers will collect the apheresis donor platelets and supply the test platelets to the hospital sites for transfusion into patients. Hospital sites will order control platelets as per their normal process, from their standard vendor. The target population for the MIPLATE study are patients with hematologic malignancies with hypoproliferative thrombocytopenia who are expected to have platelet (PLT) count(s) of ≤ 10,000/μL requiring ≥ 2 PLT transfusions. The primary objective of MIPLATE is to determine if the hemostatic efficacy of Mirasol-treated plasma stored Trima Accel® Aph PLTs are non-inferior to Conventional plasma stored Aph PLTs in subjects with hypoproliferative thrombocytopenia requiring PLT transfusions. The secondary objectives include comparing other efficacy and safety endpoints between the treatment groups. Subjects with hematologic malignancies with hypoproliferative thrombocytopenia are anticipated to experience a "transfusion episode" where they will require PLT transfusion support until bone marrow recovery. During this period all PLT transfusions required for a study subject will be given according to the subject's treatment allocation for 28 days after the initial PLT transfusion OR until transfusion independence (10 days without PLT transfusion) prior to Day 28. Additionally, serum samples for HLA antibody testing will be collected on Days 14, 28 and 56. At a minimum, the initial post-randomization prophylactic PLT transfusion will be initiated for a PLT count ≤ 10,000/µL. Thereafter, indications for PLT transfusions may be PLT count-related prophylaxis, intervention-related prophylaxis, or therapeutic (treatment of active bleeding) as determined by the treating physician(s). The indication(s) for the transfusion(s) will be captured.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
DOUBLE
Enrollment
422
The final product to be transfused to the subject will be leukoreduced (LR), apheresis (Aph) single-donor platelets (PLTs) at the standard therapeutic dose of 1 unit of Aph PLTs containing ≥ 3.0 × 1.0E11 PLTs. MIR PLTs will be treated with the Mirasol pathogen reduction technology system.
The final product to be transfused to the subject will be LR-Aph single-donor PLTs at the standard therapeutic dose of 1 unit of Aph PLTs containing ≥ 3.0 × 1.0E11 PLTs.
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Florida Health Shands Hospital
Gainesville, Florida, United States
Emory University/Children's Hospital of Atlanta
Atlanta, Georgia, United States
Days of ≥ Grade 2 Bleeding
Number of days of Grade 2 or higher bleeding recorded from treatment start date through 28 days following the first transfusion, until transfusion independence (10 days without PLT transfusion) prior to Day 28, or study termination, whichever occurred first. Subjects who obtained transfusion independence prior to Day 28 were assumed to have zero bleeding events between the date of transfusion independence and Day 28. Observed and simulated data for off-protocol transfusion intervals were included.
Time frame: From the first post-randomization platelet transfusion through 28 days following the first transfusion.
Number and Percentage of Subjects With Human Leukocyte Antigen (HLA) Alloimmunization
The outcome was the development of a new HLA Class I antibodies among subjects negative at baseline within each treatment group. Positivity for Class I HLA antibodies was determined by the 5 SD normalized background ratio cutoffs assay threshold (\>59.2, LABScreen Mixed LSM12, One Lambda).
Time frame: HLA antibodies were measured at Baseline and Days 14, 28, and 56.
Number and Percentage of Subjects With ≥ Grade 2 Bleeding
The number and percentage of subjects with at least 1 day of ≥ Grade 2 bleeding from Day 0 through Day 27 (or until transfusion independence was achieved) by treatment group
Time frame: From the first post-randomization platelet transfusion through 28 days following the first transfusion.
Number and Percentage of Subjects at the First Timepoint of ≥ Grade 2 Bleeding
The time to first ≥ Grade 2 bleeding was analyzed using a log-rank test comparing survival curves stratified by treatment group.
Time frame: From the first post-randomization platelet transfusion through 28 days following the first transfusion.
Number and Percentage of Subjects With ≥ Grade 3 Bleeding
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University of Iowa
Iowa City, Iowa, United States
John Hopkins University School of Medicine/Johns Hopkins Kimmel Cancer Center
Baltimore, Maryland, United States
Boston Children's Hospital
Boston, Massachusetts, United States
Washington University in St. Louis
St Louis, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Robert Wood Johnson Medical School/RWJ University Hospital
New Brunswick, New Jersey, United States
University of Washington Medical Center
Seattle, Washington, United States
The number and percentage of subjects with at least 1 day of ≥ Grade 3 bleeding from Day 0 through Day 27 (or until transfusion independence was achieved).
Time frame: From the first post-randomization platelet transfusion through 28 days following the first transfusion.
Number and Percentage of Subjects With PLT Refractoriness
The number and percentage of subjects with PLT refractoriness defined as 2 sequential transfusions, each with corrected count increments (CCIs) \< 5000 measured 1 hour post-transfusion.
Time frame: From the first post-randomization platelet transfusion through 28 days following the first transfusion.
Number and Percentage of Subjects With Immune Platelet Refractoriness
The number and percentage of subjects with PLT refractoriness for each treatment group. Subjects were defined as immune PLT refractoriness based on 2 sequential transfusion episodes, each with CCIs \< 5000 measured 1 hour post transfusion, and who also had a positive antibody test within 14 days before or after the onset of PLT refractoriness.
Time frame: Initial post-randomization platelet transfusion through high Class I HLA development.