Clinical trial NCT04631211: Thrombosomes® in Bleeding Thrombocytopenic Patients Study
Official title: A Prospective, Multicenter, Randomized, Open-Label Phase 2, Parallel, Dose Ranging Multidose Study of Thrombosomes® vs Liquid Stored Platelets (LSP) in Bleeding Thrombocytopenic Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Thrombocytopenia
Hematologic Malignancy
Bone Marrow Aplasia
Myeloproliferative Disorders
Myelodysplastic Syndromes
Platelet Refractoriness
Lead sponsor: Cellphire Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Department of Health and Human Services
First posted: 2020-11-17
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Dose Ranging Multidose
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Primary Efficacy Endpoint
timeFrame: Evaluated at 24 hours post initial infusion
Secondary outcomes:
measure: Secondary Efficacy Endpoint assessed by Number of days alive and without WHO (World Health Organization) Grade 2a or greater bleeding
timeFrame: 7 days after first Thrombosomes or LSP infusion
measure: Secondary Efficacy Endpoint assessed by 30 day mortality
timeFrame: 30 days post first infusion (+/- 2 days)
measure: Secondary Efficacy Endpoint assessed by cessation or decrease in bleeding, as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score
timeFrame: 24, 48, 72 hours, Day 4, Day 5, Day 6 and Day 7 post first infusion
measure: Secondary Efficacy Endpoint assessed by cessation or decrease in bleeding, as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score
timeFrame: 24, 48, 72 hours, Day 4, Day 5, Day 6 and Day 7 post first infusion
measure: Secondary Efficacy Endpoint assessed for Number, timing, type and reason for administration of all blood products
timeFrame: 7 days after first Thrombosomes or LSP infusion
measure: Secondary Efficacy Endpoint assessed by platelet count
timeFrame: 24, 48, 72 hours and Day 7 post first infusion
measure: Secondary Efficacy Endpoint assessed by measures of hematology
timeFrame: From baseline through last study visit (up to 30 days (+/- 2 days))
measure: Secondary Efficacy Endpoint assessed by measures of coagulation
timeFrame: From baseline through last study visit (up to 30 days (+/- 2 days))
measure: Secondary Efficacy Endpoint assessed by changes in markers of endothelial cell injury/repair
timeFrame: From baseline through last study visit (up to 30 days (+/- 2 days))
Other outcomes:
measure: Safety Endpoint
timeFrame: From baseline through last study visit (up to 30 days (+/- 2 days))
measure: Safety Endpoint
timeFrame: From baseline through last study visit (up to 30 days (+/- 2 days))
measure: Safety Endpoint
timeFrame: From baseline through last study visit (up to 30 days (+/- 2 days))
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Washington
country: United States
facility: Medstar Georgetown
state: District of Columbia
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Bergen
country: Norway
facility: Helse Bergen Haukeland University Hospital
Study officials:
affiliation: University of Washington
name: Terry Gernsheimer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cellphire Therapeutics, Inc.
name: Mike Fitzpatrick, PhD
role: STUDY_DIRECTOR
References: