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

Hematologic Malignancies Clinical Trial

— MIPLATE  

Official title:

Clinical Effectiveness of Conventional Versus Mirasol-treated Apheresis Platelets in Patients With Hypoproliferative Thrombocytopenia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02964325
• Other study ID #: CTS-5030
• Status: Terminated
• Phase: N/A
• Start date: May 5, 2017
• Est. completion date: June 25, 2020

Study information

• Verified date: July 2021
• Source: Terumo BCTbio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 422
• Est. completion date: June 25, 2020
• Est. primary completion date: June 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Malignancies
• Hematologic Neoplasms
• Hypoproliferative Thrombocytopenia
• Neoplasms
• Thrombocytopenia

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Emory University/Children's Hospital of Atlanta	Atlanta	Georgia
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	University of Florida Health Shands Hospital	Gainesville	Florida
United States	University of Iowa	Iowa City	Iowa
United States	Robert Wood Johnson Medical School/RWJ University Hospital	New Brunswick	New Jersey
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Washington Medical Center	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Terumo BCTbio	Biomedical Advanced Research and Development Authority

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number and Percentage of Subjects With Unanticipated Adverse Device Effects (UADEs)	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	From initial post-randomization PLT transfusion through 72 hours following the last per protocol PLT transfusion.
Primary	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.	From the first post-randomization platelet transfusion through 28 days following the first transfusion.
Secondary	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).	HLA antibodies were measured at Baseline and Days 14, 28, and 56.
Secondary	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	From the first post-randomization platelet transfusion through 28 days following the first transfusion.
Secondary	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.	From the first post-randomization platelet transfusion through 28 days following the first transfusion.
Secondary	Number and Percentage of Subjects With = Grade 3 Bleeding	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).	From the first post-randomization platelet transfusion through 28 days following the first transfusion.
Secondary	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.	From the first post-randomization platelet transfusion through 28 days following the first transfusion.
Secondary	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.	Initial post-randomization platelet transfusion through high Class I HLA development.