Thrombosomes® in Bleeding Thrombocytopenic Patients

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

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

Study Overview

• Status: Completed
• Conditions: Hematologic Diseases; Thrombocytopenia; Bone Marrow Aplasia
• Intervention / Treatment: Biological: Thrombosomes

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway
    • Haukeland University Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Georgetown University Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth Hitchcock Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Hoxworth Blood Center/University of Cincinnati
  • Texas
    • Houston, Texas, United States, 77092
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cellphire Therapeutics, Inc.
• Collaborators: Department of Health and Human Services

Publications and helpful links

General Publications

• Ohanian M, Cancelas JA, Davenport R, Pullarkat V, Hervig T, Broome C, Marek K, Kelly M, Gul Z, Rugg N, Nestheide S, Kinne B, Szczepiorkowski Z, Kantarjian H, Pehta J, Biehl R, Yu A, Aung F, Antebi B, Fitzpatrick GM. Freeze-dried platelets are a promising alternative in bleeding thrombocytopenic patients with hematological malignancies. Am J Hematol. 2022 Mar 1;97(3):256-266. doi: 10.1002/ajh.26403. Epub 2021 Dec 23.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2018
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): September 25, 2019

Study Registration Dates

• First Submitted: January 3, 2018
• First Submitted That Met QC Criteria: January 8, 2018
• First Posted (Actual): January 9, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: bleeding; thrombocytopenia
• Additional Relevant MeSH Terms: Pathologic Processes; Bone Marrow Diseases; Anemia; Blood Platelet Disorders; Bone Marrow Failure Disorders; Hemorrhage; Hematologic Diseases; Thrombocytopenia; Anemia, Aplastic
• Other Study ID Numbers: 2017-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No