A Phase I, Multi-Center, Open-Label, Dose Escalation Study of Thrombosomes® in Bleeding Thrombocytopenic Patients in Three Cohorts
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 24
- Locations
- 7
- Primary Endpoint
- Number of Patients With Treatment-Emergent Serious Adverse Events (TESAE)
Study Overview
Brief Summary
The study evaluates the safety and potential early signals of efficacy of allogeneic Thrombosomes in bleeding thrombocytopenic patients
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 74 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
3.78 x10^8 Thrombosomes/kg
Cohort 3
Intervention: Thrombosomes (Biological)
1.89 x 10^8 Thrombosomes/kg
Cohort 2
Intervention: Thrombosomes (Biological)
9.45 x 10^7 Thrombosomes/kg
Cohort 1
Intervention: Thrombosomes (Biological)
Outcomes
Primary Outcomes
Number of Patients With Treatment-Emergent Serious Adverse Events (TESAE)
Time Frame: 30 days
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).
Number of Patients With Treatment-Emergent Adverse Events (TEAE)
Time Frame: 30 days
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).
Secondary Outcomes
- Number of Patients With Grade-level Change in WHO Bleeding Assessment Score From Baseline - Patients WHO Score at Primary Bleeding Site(Baseline, 1, 6, 24 hours, and Day 6 post infusion)
- Number of Patients With a Shift From Baseline in Hemoglobin(1, 6, 24 hours, Day 3, 4, 5, and 6 post infusion)
- Number of Patients With a Shift From Baseline in Hematocrit(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(24 hours post infusion)
- Number of WHO Bleeding Sites With Status Change From Baseline(1, 6, 24 hours, and Day 6 post infusion)
- Median Platelet Counts(Screening, Baseline, 1, 6, 24 hours, Day 3, 4, 5, and 6 post infusion)