Efficacy of Mirasol-treated Apheresis Platelets in Patients With Hypoproliferative Thrombocytopenia (MIPLATE)

• ClinicalTrials.gov Identifier: NCT02964325
• Recruitment Status: Terminated
• First Posted: November 16, 2016
• Results First Posted: July 16, 2021
• Last Update Posted: August 19, 2021
• Sponsor: Terumo BCTbio
• Collaborator: Biomedical Advanced Research and Development Authority
• Information provided by (Responsible Party): Terumo BCTbio

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hematologic Malignancies; Hypoproliferative Thrombocytopenia	Device: Mirasol platelets (MIR PLTs); Device: Reference platelets (REF PLTs)	Not Applicable

Detailed Description:

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 422 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Masking Description: Though this is not a blinded study, treatment assignment is obtained through electronic system and should not be shared those performing the primary outcome assessment or assessors of adverse events.
• Primary Purpose: Supportive Care
• Official Title: Clinical Effectiveness of Conventional Versus Mirasol-treated Apheresis Platelets in Patients With Hypoproliferative Thrombocytopenia
• Actual Study Start Date: May 5, 2017
• Actual Primary Completion Date: June 25, 2020
• Actual Study Completion Date: June 25, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Mirasol platelets (MIR PLTs); Leukoreduced, Trima Accel® apheresis platelets stored in 100% plasma, pathogen reduced with the Mirasol® Pathogen Reduction Technology (PRT) System	Device: Mirasol platelets (MIR PLTs); 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.
Active Comparator: Reference platelets (REF PLTs); Leukoreduced, apheresis platelets stored in 100% plasma	Device: Reference platelets (REF PLTs); 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.

Outcome Measures

Primary Outcome Measures :

1. Days of ≥ Grade 2 Bleeding [ Time Frame: From the first post-randomization platelet transfusion through 28 days following the first transfusion. ]
   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.

Secondary Outcome Measures :

1. Number and Percentage of Subjects With Human Leukocyte Antigen (HLA) Alloimmunization [ Time Frame: HLA antibodies were measured at Baseline and Days 14, 28, and 56. ]
   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).
2. Number and Percentage of Subjects With ≥ Grade 2 Bleeding [ Time Frame: From the first post-randomization platelet transfusion through 28 days following the first transfusion. ]
   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
3. Number and Percentage of Subjects at the First Timepoint of ≥ Grade 2 Bleeding [ Time Frame: From the first post-randomization platelet transfusion through 28 days following the first transfusion. ]
   The time to first ≥ Grade 2 bleeding was analyzed using a log-rank test comparing survival curves stratified by treatment group.
4. Number and Percentage of Subjects With ≥ Grade 3 Bleeding [ Time Frame: From the first post-randomization platelet transfusion through 28 days following the first transfusion. ]
   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).
5. Number and Percentage of Subjects With PLT Refractoriness [ Time Frame: From the first post-randomization platelet transfusion through 28 days following the first transfusion. ]
   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.
6. Number and Percentage of Subjects With Immune Platelet Refractoriness [ Time Frame: Initial post-randomization platelet transfusion through high Class I HLA development. ]
   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.

Other Outcome Measures:

1. Number and Percentage of Subjects With Unanticipated Adverse Device Effects (UADEs) [ Time Frame: From initial post-randomization PLT transfusion through 72 hours following the last per protocol PLT transfusion. ]
   UADEs are identified as treatment emergent adverse events reported by the investigator as serious, unanticipated, at least possibly related to study device or at least possibly related to treatment. UADEs were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 19.1

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Weight > 10 kg (22 lbs)
2. Subject has a hematologic malignancy with hypoproliferative thrombocytopenia and is expected to have PLT count(s) ≤ 10,000/µL requiring ≥ 2 PLT transfusions

3. Laboratory results within 5 days prior to anticipated initiation of the first post randomization PLT transfusion:

   1. Prothrombin time (PT) and/or international normalized ratio (INR) ≤ 1.3 × the upper limit of normal (ULN)
   2. Activated partial thromboplastin time (aPTT) ≤ 1.3 × ULN
   3. Fibrinogen ≥ 100 mg/dL
4. Women of childbearing potential must have a negative pregnancy test and agree to practice a medically acceptable contraception regimen for the study duration. Women who are postmenopausal for at least 1 year (> 12 months since last menses) or are surgically sterilized do not require this test
5. IC from the subject or assent from the subject and consent from a parent or guardian, if the subject is < 18 years of age

Exclusion Criteria:

1. Treatment with pathogen-reduced blood products within previous 6 months
2. Subject has been previously enrolled in this study and received at least 1 per protocol PLT transfusion
3. a.) Subject is receiving therapeutic doses of antiplatelet agents, antifibrinolytics, and/or PLT specific growth factors within 10 days prior to randomization or b.) Subject is receiving therapeutic doses of anticoagulant, pro-coagulant or antithrombotic agents within 10 days prior to randomization. Subjects can be included if receiving the following: prophylactic dosing of anticoagulants (heparin, any low molecular weight heparin, enoxaparin, or fondaparinux), anticoagulants/thrombolytic agents used to maintain or re-establish the patency of catheters (heparin flushes or tissue-plasminogen activase [TPA], therapeutic doses of anticoagulants with a half-life of < 24 hours if it will be discontinued at least 24 hours prior to the first study transfusion, single periprocedural doses of anticoagulants with a half-life of < 24 hours or low dose aspirin (81 mg per day)
4. Subject has ≥ grade 2 bleeding at the time of randomization
5. Planned administration of bedside LR PLT transfusion(s)
6. Presently with or a history of acute promyelocytic leukemia (APML), idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), or hemolytic uremic syndrome (HUS)
7. HLA and/or HPA-alloimmunization and/or platelet refractory as determined by the investigator
8. Hypersplenism as evidenced by splenomegaly based on investigator assessment at baseline
9. History or diagnosis of a disease affecting hemostasis
10. Currently taking, or participating in a clinical study involving PLT substitutes, PLT growth factors, or pharmacologic agents intended to enhance (i.e, antifibrinolytic agents) or decrease PLT hemostatic function
11. Acute or chronic medical disorder that, in the opinion of the investigator, would impair the ability of the subject to receive protocol treatment
12. Subject is pregnant or lactating
13. Inability of the subject to comply with study procedures and/or follow-up

Contacts and Locations

Locations

United States, District of Columbia

Children's National Medical Center

Washington, District of Columbia, United States, 20010

United States, Florida

University of Florida Health Shands Hospital

Gainesville, Florida, United States, 32608

United States, Georgia

Emory University/Children's Hospital of Atlanta

Atlanta, Georgia, United States, 30322

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Maryland

John Hopkins University School of Medicine/Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, United States, 21231

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

United States, Missouri

Washington University in St. Louis

Saint Louis, Missouri, United States, 63110

United States, Nebraska

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198

United States, New Jersey

Robert Wood Johnson Medical School/RWJ University Hospital

New Brunswick, New Jersey, United States, 08903

United States, Washington

University of Washington Medical Center

Seattle, Washington, United States, 98109

Sponsors and Collaborators

Terumo BCTbio

Biomedical Advanced Research and Development Authority

Investigators

• Study Director: Robert Cortes, MD; Terumo BCT
• Principal Investigator: Sherrill Slichter, MD; Bloodworks Northwest

  Study Documents (Full-Text)

Documents provided by Terumo BCTbio:

Study Protocol  [PDF] January 30, 2019

Statistical Analysis Plan  [PDF] September 2, 2020

More Information

• Responsible Party: Terumo BCTbio
• ClinicalTrials.gov Identifier: NCT02964325
• Other Study ID Numbers: CTS-5030
• First Posted: November 16, 2016
• Results First Posted: July 16, 2021
• Last Update Posted: August 19, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Terumo BCTbio:

hypoproliferative thrombocytopenia; hematologic malignancies; thrombocytopenia; platelet therapy; apheresis; pathogen reduction therapy

Additional relevant MeSH terms:

Neoplasms; Hematologic Neoplasms; Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Neoplasms by Site