Thrombosomes® in Bleeding Thrombocytopenic Patients Study

A Prospective, Multicenter, Randomized, Open-Label Phase 2, Parallel, Dose Ranging Multidose Study of Thrombosomes® vs Liquid Stored Platelets (LSP) in Bleeding Thrombocytopenic Patients

This prospective, multicenter, randomized, open-label, Phase 2, parallel, dose ranging, multidose trial will enroll patients into 3 Thrombosomes dose groups and 1 control liquid stored platelets (LSP) group in order to evaluate, in a dose-escalation manner, the safety, and impact on bleeding, and the preliminary effect on coagulation measures of increasing doses of allogeneic Thrombosomes in comparison to standard of care, LSP.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes; Myeloproliferative Disorders; Thrombocytopenia; Hematologic Malignancy; Bone Marrow Aplasia; Platelet Refractoriness
• Intervention / Treatment: Biological: Thrombosomes; Biological: Liquid Stored Platelets (LSP)

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Expanded Access

Temporarily not available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • Rambam Medical Center
• Norway
  • Bergen, Norway
    • Helse Bergen Haukeland University Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adults (≥18 years) with TCP as defined by BOTH (a) and (b):

   1. a platlet count of ≤ 70,000 platelets/μL blood

   2. ANY ONE OR MORE of (1-3):

      1. confirmed diagnosis of hematologic malignancy, myeloproliferative disorder, myelodysplastic syndrome, or aplasia
      2. undergoing chemotherapy, immunotherapy, radiation therapy or hematopoietic stem cell transplantation
      3. refractory to platelet transfusion defined as two 1-hour CCI of <5,000 on consecutive transfusions of LSP or as defined by local site policy (Sacher, 2003)
2. WHO Bleeding Score of 2 or 3
3. Able to provide informed consent directly or through legally authorized representative, and comply with treatment and monitoring
4. Negative pregnancy test for women of childbearing potential

Exclusion Criteria:

1. Any disorder or condition related to any venous thrombosis, embolism, or ischemia within the past 3 months
2. Any disorder or condition related to arterial thrombosis including: ischemia, stroke, MI, or stent placement, within past 6 months
3. Any valve replacement and/or repair of left atrial appendance occlusion device
4. Sinusoidal obstruction syndrom (veno-occlusive disease) or cytopkine release syndrome associated with CAR-T cell therapy
5. Refusal to accept blood products
6. Liver enzyme blood levels greater than 3× the upper limit of normal (ULN)
7. Blood creatinine level greater than 3× ULN
8. Received platelet inhibitor drugs, cyclooxygenase-2 (COX-2) inhibitors, or nonsteroidal anti-inflammatory drugs within 5 days prior to infusion
9. Currently (at the time of randomization) receiving anticoagulant therapy or antiplatelet therapy. Low dose prophylaxis for line clots is not excluded.
10. Receipt of any pro-coagulant agents (e.g., DDAVP, recombinant Factor VIIa or prothrombin complex concentrates (PCC)) other than Tranexamic Acid (TXA) or Epsilon Aminocaproic Acid (EACA, Amicar), within 48 hours of first infusion, or with known hypercoagulable state
11. WHO Bleeding Score of 2 solely due to lumbar puncture, retinal bleeding or GI bleeding or WHO Bleeding Score of 3 solely due to lumbar puncture
12. Receiving L-asparaginase as part of a current cycle of treatment
13. Known inherited or acquired bleeding disorder including, but not limited to: acquired storage pool deficiency or paraproteinemia with platelet inhibition
14. Known inherited or acquired prothrombotic disorders, including antiphospholipid syndrome (Those with lupus anticoagulant or positive antiphospholipid serology without thrombosis are NOT excluded.)
15. Anuria
16. On dialysis
17. Receipt of an investigational drug within 1 month before first infusion, other than for treatment of their underlying disease
18. Females pregnant or nursing or unwilling to use contraception during and for 30 days after taking the study product (females). Evidence of effective birth control may be used, at the discretion of the physician
19. Acute or chronic medical disorder that, in the opinion of the Investigator, would impair the ability of the patient to receive or respond to study treatment
20. Prior participation in this study with successful infusion of the investigational or control product
21. Currently enrolled in other trials not related to their primary disease process or involving platelet transfusions, platelet growth factors, or other pro-coagulant agents

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Thrombosomes Low Dose	Biological: Thrombosomes; Human platelet derived lyophilized hemostatic
Experimental: Thrombosomes Medium Dose	Biological: Thrombosomes; Human platelet derived lyophilized hemostatic
Experimental: Thrombosomes High Dose	Biological: Thrombosomes; Human platelet derived lyophilized hemostatic
Active Comparator: Liquid Stored Platelets (Control)	Biological: Liquid Stored Platelets (LSP); Leukocyte reduced apheresis platelets or whole blood derived pooled platelet concentrate equivalent (4-6 units)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy Endpoint	Cessation or decrease in bleeding at primary bleeding site, based upon the most severe bleeding location at Day 1 baseline taken with in 12 hours prior to infusion, as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score evaluated at 24 hours post initial infusion.	Evaluated at 24 hours post initial infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Efficacy Endpoint assessed by Number of days alive and without WHO (World Health Organization) Grade 2a or greater bleeding	Number of days alive and without WHO (World Health Organization) Grade 2 or greater bleeding through initial 7 days after first Thrombosomes or LSP Infusion	7 days after first Thrombosomes or LSP infusion
Secondary Efficacy Endpoint assessed by 30 day mortality	30-day mortality post first infusion of Thrombosomes or post first infusion of LSP as control	30 days post first infusion (+/- 2 days)
Secondary Efficacy Endpoint assessed by cessation or decrease in bleeding, as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score	Cessation or decrease in primary bleeding site, as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score at 24, 48, 72 hours, Day 4, Day 5, Day 6 and Day 7 after first infusion of Thrombosomes or LSP infusion as control.	24, 48, 72 hours, Day 4, Day 5, Day 6 and Day 7 post first infusion
Secondary Efficacy Endpoint assessed by cessation or decrease in bleeding, as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score	Cessation or decrease in each additional bleeding site (other than primary bleeding site), as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score at 24, 48, 72 hours, Day 4, Day 5, Day 6 and Day 7 after first infusion of Thrombosomes or LSP infusion as control.	24, 48, 72 hours, Day 4, Day 5, Day 6 and Day 7 post first infusion
Secondary Efficacy Endpoint assessed for Number, timing, type and reason for administration of all blood products	Number, timing, type and reason for administration of all blood products including platelets and Thrombosomes during the initial 7 days after first Thrombosomes or LSP infusion	7 days after first Thrombosomes or LSP infusion
Secondary Efficacy Endpoint assessed by platelet count	Platelet count measured at 24, 48, 72 hours and Day 7 of first infusion of Thrombosomes or LSP. Also evaluate at Day 4-6 if patient is hospitalized at that time.	24, 48, 72 hours and Day 7 post first infusion
Secondary Efficacy Endpoint assessed by measures of hematology	Measures of hematology including: Prothrombin Fragment 1+2; thrombin generation assay (TGA); Thrombopoietin; activated Protein C, tissue plasminogen activator (TPA), and plasminogen activator inhibitor (PAI) per schedule of assessments	From baseline through last study visit (up to 30 days (+/- 2 days))
Secondary Efficacy Endpoint assessed by measures of coagulation	Measures of coagulation including: prothrombin time (PT); international normalized ratio (INR); fibrinogen; D-dimer; activated partial thromboplastin time (aPTT); and thromboelastography (TEG) or rotational thromboelastometry (ROTEM) per schedule of assessments	From baseline through last study visit (up to 30 days (+/- 2 days))
Secondary Efficacy Endpoint assessed by changes in markers of endothelial cell injury/repair	Changes in markers of endothelial cell injury/repair from preinfusion baseline through 72 hours after first infusion, including: Syndecan-1, hyaluronan, thrombomodulin, vascular endothelial growth factor (VEGF), interleukin 6, sVE cadherin per schedule of assessments.	From baseline through last study visit (up to 30 days (+/- 2 days))

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Endpoint	Serious Adverse Events (SAEs)	From baseline through last study visit (up to 30 days (+/- 2 days))
Safety Endpoint	Adverse Events (AEs)	From baseline through last study visit (up to 30 days (+/- 2 days))
Safety Endpoint	Unanticipated problems involving risk to human subjects	From baseline through last study visit (up to 30 days (+/- 2 days))

Collaborators and Investigators

• Sponsor: Cellphire Therapeutics, Inc.
• Collaborators: Department of Health and Human Services
• Investigators: Study Director: Mike Fitzpatrick, PhD, Cellphire Therapeutics, Inc.; Principal Investigator: Terry Gernsheimer, MD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Actual): January 7, 2022
• Study Completion (Actual): January 7, 2022

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 17, 2020

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Anemia; Blood Platelet Disorders; Bone Marrow Failure Disorders; Myelodysplastic Syndromes; Hematologic Neoplasms; Thrombocytopenia; Myeloproliferative Disorders; Anemia, Aplastic
• Other Study ID Numbers: #2019-1

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