Thrombosomes® in Bleeding Thrombocytopenic Patients

Study Overview
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Brief Summary
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The study evaluates the safety and potential early signals of efficacy of allogeneic Thrombosomes in bleeding thrombocytopenic patients

Detailed Description
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The primary objective of the present study was to assess the safety of increasing dose levels of Thrombosomes in bleeding patients with thrombocytopenia. The secondary objective was to explore early signals of clinical efficacy of Thrombosomes in this population. The secondary objectives included: 1) Evaluation of the impact on WHO (World Health Organization) bleeding scores at various timepoints; 2) number and type of blood products infused through day 6 follow-up period; and 3) post hoc analysis of hematology, coagulation, and chemistry.

Official Title
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A Phase I, Multi-Center, Open-Label, Dose Escalation Study of Thrombosomes® in Bleeding Thrombocytopenic Patients in Three Cohorts

Conditions
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Bone Marrow Aplasia, Thrombocytopenia, Hematologic Diseases

Intervention / Treatment
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* Biological: Thrombosomes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults up to 74 y/o with any of following: acute leukemia (ALL or AML), myelodysplasia, aplasia, and/or therapy (chemotherapy or radiation) induced bone marrow aplasia or hypoplasia with thrombocytopenia (platelet count ≥ 5,000 and ≤ 70,000/μL) for a minimum of 2 days. May include bone marrow transplant or peripheral or cord blood stem cell recipients, but not subjects with Graft-vs-Host disease. Hospitalized patients (or willing to be hospitalized for 24 hours after Rx) with Modified WHO Grade 1 (subset) or Grade 2 Bleeding Score or at risk for same within 4 weeks of screening. The Grade 1 subset includes patients who have either epistaxis, hematuria, oral petechiae, or bleeding at invasive or other wound sites. No platelet inhibitor drugs within 5 days prior to infusion and through Day 6 follow-up period. Exclusion Criteria: History or condition related to thrombosis, embolism or vascular occlusion/ischemia, including but not limited to: transient ischemic attack, stroke, myocardial infarction, stent placement, valve replacement and/or repair Currently with an active acute infection, or suspected infection, a single oral temperature of ≥ 101° F or a temperature of ≥ 100.4°F sustained over a 1 h period in past 24 h. Subjects on prophylactic antibiotics are not excluded from study Coagulopathy or receiving anticoagulants that result in PT (prothrombin time) or aPTT (activated partial thromboplastin time) values greater than 1.3 X upper limit of normal or elevated D-dimer of decreased fibrinogen History of any inherited coagulation or platelet function, disorder or ITP (idiopathic thrombocytopenic purpura), TTP (thrombotic thrombocytopenic purpura), or HUS (hemolytic-uremic syndrome) Receipt of tranexamic acid or other antifibrinolytics within 48 hrs prior to infusion Treatment with an investigational drug within 1 month of infusion, other than for treatment of their underlying disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 9.45 x 10^7 Thrombosomes/kg<br>Cohort 1 | Biological: Thrombosomes<br>* Freeze-dried platelets<br>|
| Experimental: 1.89 x 10^8 Thrombosomes/kg<br>Cohort 2 | Biological: Thrombosomes<br>* Freeze-dried platelets<br>|
| Experimental: 3.78 x10^8 Thrombosomes/kg<br>Cohort 3 | Biological: Thrombosomes<br>* Freeze-dried platelets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Treatment-Emergent Adverse Events (TEAE) | Overall frequency of (and number and percentage of patients who experience) TEAEs including serious adverse drug reactions and treatment-related events specifically defining the study's suspension and stopping rules (i.e., thromboembolic events, acute lung injury, anaphylaxis, and death). | 30 days | 
| Number of Patients With Treatment-Emergent Serious Adverse Events (TESAE) | Overall frequency of (and number and percentage of patients who experience) TESAEs including serious adverse drug reactions and treatment-related events specifically defining the study's suspension and stopping rules (i.e., thromboembolic events, acute lung injury, anaphylaxis, and death). | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of WHO Bleeding Sites With Status Change From Baseline | Grade-level change in WHO bleeding assessment score at most severe bleeding site from baseline; WHO bleeding assessment score ranges from 1 to 4, with higher numbers indicating worse bleeding. | 1, 6, 24 hours, and Day 6 post infusion | 
| Number of Patients With Grade-level Change in WHO Bleeding Assessment Score From Baseline - Patients WHO Score at Primary Bleeding Site | Patients WHO score at primary bleeding site. WHO bleeding assessment score ranges from 1 to 4, with higher numbers indicating worse bleeding. The maximum WHO bleeding assessment score for patients on study was 2. | Baseline, 1, 6, 24 hours, and Day 6 post infusion | 
| Number of Patients With a Shift From Baseline in Hemoglobin | Shift from baseline clinical status of hemoglobin measure at different timepoints post infusion | 1, 6, 24 hours, Day 3, 4, 5, and 6 post infusion | 
| Number of Patients With a Shift From Baseline in Hematocrit | Shift from baseline clinical status of hematocrit measure at different timepoints post infusion | 1, 6, 24 hours, Day 3, 4, 5, and 6 post infusion | 
| Number or Patients With a Shift From Baseline in Coagulation Measures 24 Hours Post Infusion | Shift from baseline clinical status of coagulation measure at 24 hours post infusion for each cohort | 24 hours post infusion | 
| Median Platelet Counts | Median Platelet Counts Per Time Point | Screening, Baseline, 1, 6, 24 hours, Day 3, 4, 5, and 6 post infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thrombocytopenia, bleeding