Phase 1 Safety Study of Dimethyl Sulfoxide Cryopreserved Platelets

Study Overview
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Brief Summary
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This study is to evaluate the safety of intravenous (IV) infusion of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP) in participants with World Health Organization (WHO) Grade 2 bleed in spite of receiving a transfusion of liquid stored platelets (LSP) in the past 48 hours by collecting adverse events (AEs) and by evaluating coagulation-related parameters to assess the evidence of any thrombotic events after CPP or LSP transfusion.

Detailed Description
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After determining eligibility for study participation, 4 sequential cohorts of subjects will receive escalating doses of CPP (Test) or 1 unit of LSP (Control) randomized 6:1 within each cohort. Each sequential cohort will receive the following transfusions starting with the first cohort: 0.5, 1, 2, and 3 units of CPP with an additional single subject in each cohort who will receive 1 unit of LSP for a total of 28 subjects. Assignment to Test and Control platelets for subjects in each cohort will be centrally randomized using an interactive web response system (IWRS). Following the study transfusion, subjects are followed for evidence of transfusion reactions, thrombotic events, other AEs, coagulation-related parameters, and platelet efficacy endpoints. CPP or LSP will be transfused into a patient according to the randomized product and dose assignment within the cohort. Following the transfusion, subjects are followed for the remainder of Study Day 1 and on Study Day 2 for AEs and tested for coagulation markers including fibrinogen, D-dimer, prothrombin fragments 1 + 2 (F 1+2), thrombin antithrombin (TAT), anti-thrombin (AT), prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin generation testing (TGT) results, thromboelastography (TEG) results, and other potential complications of platelet transfusion such as transfusion reactions and thrombotic events including assessment of vital signs (blood pressure, heart rate, respiration rate, and pulse oximetry). A subject is considered to have completed the study for safety evaluation for dose escalation, if he/she receives a study infusion and completed study-related Day 3 procedures.

Official Title
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Dose Escalation Study Evaluating the Safety of Dimethyl Sulfoxide Cryopreserved Platelets Compared With Liquid Stored Platelets in Patients With Uncontrolled Bleeding

Conditions
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Thrombocytopenia

Intervention / Treatment
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* Biological: CPP
* Biological: LSP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, at least 18 years of age. Ability to comprehend the study procedures and signed informed consent. If pre-menopausal female, must have a negative serum pregnancy test, and, if of child bearing potential, must be using an acceptable method of contraception. Diagnosed with any the following: acute leukemia (ALL or AML), chronic leukemia (CML, CLL, CMML, or hairy cell leukemia), myelodysplasia, aplasia, hematopoietic or non-hematopoietic solid tumor, or therapy (chemotherapy or radiation) induced bone marrow aplasia or hypoplasia. Either autologous or allogeneic bone marrow transplant or peripheral or cord blood stem cell recipients may be enrolled. WHO grade 2 or greater bleeding. Exclusion Criteria: Acute or chronic DIC as evidence by D-dimer greater than 8 μg/mL and fibrinogen less than 100 mg (0.1 g)/dL. Both criteria must be met. If data are in the medical record for fibrin degradation products (FDPs), then FDP must be <=40 μg/mL (FDP >40 μg/mL is indicative of DIC). PT or aPTT > 1.3 times the upper limit of normal for the laboratory. History of major operative procedures that required general anesthesia in the past 2 weeks. History of any prior major unprovoked thrombotic events and/or known inherited disorder of coagulation or platelet function (by history) (not to include clots in catheters, etc). A history or diagnosis of immune thrombocytopenia, thrombotic thrombocytopenic purpura, or hemolytic uremic syndrome. Females who are breastfeeding. Veno-occlusive disease or possible veno-occlusive disease. Receiving active, inpatient treatment with anti-platelet drugs and/or full anticoagulation therapy. Note: a heparin flush may be given daily and before and after blood draws to patients with a central line to keep the line patent. Subject previously enrolled in this study and received a study transfusion.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 with 0.5 units of CPP<br>A single 30 to 60 minute intravenous (IV) infusion of 0.5 unit of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP) | Biological: CPP<br>* One unit of frozen CPP contains approximately 3.4 x 10^11 irradiated platelets and approximately 6% DMSO in sterile 0.9% sodium chloride solution (total volume of 20 mL to 35 mL) stored frozen at ≤ -65°C.<br>* Other names: dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP);|
| Active Comparator: Cohort 1 with 1 unit of LSP<br>A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP) | Biological: LSP<br> <br> * Other names: liquid stored platelets (LSP);|
| Experimental: Cohort 2 with 1 unit of CPP<br>A single 30 to 60 minute intravenous (IV) infusion of 1 unit of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP) | Biological: CPP<br>* One unit of frozen CPP contains approximately 3.4 x 10^11 irradiated platelets and approximately 6% DMSO in sterile 0.9% sodium chloride solution (total volume of 20 mL to 35 mL) stored frozen at ≤ -65°C.<br>* Other names: dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP);|
| Active Comparator: Cohort 2 with 1 unit of LSP<br>A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP) | Biological: LSP<br> <br> * Other names: liquid stored platelets (LSP);|
| Experimental: Cohort 3 with 2 units of CPP<br>A single 30 to 60 minute intravenous (IV) infusion of 2 units of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP) | Biological: CPP<br>* One unit of frozen CPP contains approximately 3.4 x 10^11 irradiated platelets and approximately 6% DMSO in sterile 0.9% sodium chloride solution (total volume of 20 mL to 35 mL) stored frozen at ≤ -65°C.<br>* Other names: dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP);|
| Active Comparator: Cohort 3 with 1 unit of LSP<br>A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP) | Biological: LSP<br> <br> * Other names: liquid stored platelets (LSP);|
| Experimental: Cohort 4 with 3 units of CPP<br>A single 30 to 60 minute intravenous (IV) infusion of 3 units of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP) | Biological: CPP<br>* One unit of frozen CPP contains approximately 3.4 x 10^11 irradiated platelets and approximately 6% DMSO in sterile 0.9% sodium chloride solution (total volume of 20 mL to 35 mL) stored frozen at ≤ -65°C.<br>* Other names: dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP);|
| Active Comparator: Cohort 4 with 1 unit of LSP<br>A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP | Biological: LSP<br> <br> * Other names: liquid stored platelets (LSP);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) by Level of Severity | Clinical laboratory [chemistry (serum creatinine, lactate dehydrogenase (LDH), and troponin, and hematology (hemoglobin and hematocrit)] parameters, physical examination findings, electrocardiogram (ECG)] and vital sign AEs summarized by severity. | day of thru 6 days after transfusion | 
| Number of Subject Who Experienced Adverse Events (AEs) for a Specific Severity | Number of subjects who experienced AEs at specific levels of severity. Clinical laboratory [chemistry (serum creatinine, lactate dehydrogenase (LDH), and troponin, and hematology (hemoglobin and hematocrit)] parameters, physical examination findings, electrocardiogram (ECG)] and vital signs were evaluated. | day of thru 6 days after transfusion | 
| Number of Subject With Thrombotic Events | Subjects with any signs or symptoms of thrombotic events. | 6 days after transfusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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platelet transfusion