Back to resultsPhase 1 Safety Study of Dimethyl Sulfoxide Cryopreserved Platelets
Primary Purpose
Thrombocytopenia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CPP
LSP
Sponsored by
About this trial
This is an interventional treatment trial for Thrombocytopenia focused on measuring platelet transfusion
Eligibility Criteria
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.
Sites / Locations
- Dartmouth-Hitchcock Medical Center
- Hoxworth Blood Center
- Puget Sound Blood Center
- University of Washington, Division of Hematology
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Experimental
Active Comparator
Experimental
Active Comparator
Experimental
Active Comparator
Experimental
Active Comparator
Arm Label
Cohort 1 with 0.5 units of CPP
Cohort 1 with 1 unit of LSP
Cohort 2 with 1 unit of CPP
Cohort 2 with 1 unit of LSP
Cohort 3 with 2 units of CPP
Cohort 3 with 1 unit of LSP
Cohort 4 with 3 units of CPP
Cohort 4 with 1 unit of LSP
Arm Description
A single 30 to 60 minute intravenous (IV) infusion of 0.5 unit of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP)
A single 30 to 60 minute intravenous (IV) infusion of 1 unit of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP)
A single 30 to 60 minute intravenous (IV) infusion of 2 units of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP)
A single 30 to 60 minute intravenous (IV) infusion of 3 units of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP
Outcomes
Primary Outcome Measures
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.
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.
Number of Subject With Thrombotic Events
Subjects with any signs or symptoms of thrombotic events.
Secondary Outcome Measures
Full Information
NCT ID
NCT02078284
First Posted
February 26, 2014
Last Updated
May 19, 2021
Sponsor
U.S. Army Medical Research and Development Command
1. Study Identification
Unique Protocol Identification Number
NCT02078284
Brief Title
Phase 1 Safety Study of Dimethyl Sulfoxide Cryopreserved Platelets
Official Title
Dose Escalation Study Evaluating the Safety of Dimethyl Sulfoxide Cryopreserved Platelets Compared With Liquid Stored Platelets in Patients With Uncontrolled Bleeding
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
November 5, 2014 (Actual)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 17, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
U.S. Army Medical Research and Development Command
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombocytopenia
Keywords
platelet transfusion
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 with 0.5 units of CPP
Arm Type
Experimental
Arm Description
A single 30 to 60 minute intravenous (IV) infusion of 0.5 unit of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
Arm Title
Cohort 1 with 1 unit of LSP
Arm Type
Active Comparator
Arm Description
A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP)
Arm Title
Cohort 2 with 1 unit of CPP
Arm Type
Experimental
Arm Description
A single 30 to 60 minute intravenous (IV) infusion of 1 unit of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
Arm Title
Cohort 2 with 1 unit of LSP
Arm Type
Active Comparator
Arm Description
A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP)
Arm Title
Cohort 3 with 2 units of CPP
Arm Type
Experimental
Arm Description
A single 30 to 60 minute intravenous (IV) infusion of 2 units of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
Arm Title
Cohort 3 with 1 unit of LSP
Arm Type
Active Comparator
Arm Description
A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP)
Arm Title
Cohort 4 with 3 units of CPP
Arm Type
Experimental
Arm Description
A single 30 to 60 minute intravenous (IV) infusion of 3 units of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
Arm Title
Cohort 4 with 1 unit of LSP
Arm Type
Active Comparator
Arm Description
A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP
Intervention Type
Biological
Intervention Name(s)
CPP
Other Intervention Name(s)
dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
LSP
Other Intervention Name(s)
liquid stored platelets (LSP)
Primary Outcome Measure Information:
Title
Adverse Events (AEs) by Level of Severity
Description
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.
Time Frame
day of thru 6 days after transfusion
Title
Number of Subject Who Experienced Adverse Events (AEs) for a Specific Severity
Description
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.
Time Frame
day of thru 6 days after transfusion
Title
Number of Subject With Thrombotic Events
Description
Subjects with any signs or symptoms of thrombotic events.
Time Frame
6 days after transfusion
Other Pre-specified Outcome Measures:
Title
Corrected Count Increments (CCI)
Description
Corrected Count Increments Expressed in units of mm^2/(µL*10¹¹ platelets) (CCI) in the 6 hour period after the study platelet transfusion and on Day 2 (approximately 24 hours after the study platelet transfusion)
Time Frame
Day 1 up to 6 hrs after transfusion and Day 2 approx 24 hrs after transfusion
Title
Count Increment
Description
Count Increment expressed in units of platelets (x10^3 µL) (CI)
Time Frame
On Day 1 up to 6 hours after transfusion and on Day 2 approximately 24 hours after transfusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sherrill J Slichter, MD
Organizational Affiliation
Bloodworks
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Terry B Gernsheimer, MD
Organizational Affiliation
University of Washington, Division of Hematology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zbigniew Szczepiorkowski, MD, PhD
Organizational Affiliation
Center for Transfusion Medicine Research, Lebanon, NH
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jose A Cancelas-Perez, MD, PhD
Organizational Affiliation
Hoxworth Blood Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Hoxworth Blood Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Puget Sound Blood Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
University of Washington, Division of Hematology
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30204953
Citation
Slichter SJ, Dumont LJ, Cancelas JA, Jones M, Gernsheimer TB, Szczepiorkowski ZM, Dunbar NM, Prakash G, Medlin S, Rugg N, Kinne B, Macdonald VW, Housler G, Valiyaveettil M, Hmel P, Ransom JH. Safety and efficacy of cryopreserved platelets in bleeding patients with thrombocytopenia. Transfusion. 2018 Sep;58(9):2129-2138. doi: 10.1111/trf.14780.
Results Reference
derived
Learn more about this trial
Phase 1 Safety Study of Dimethyl Sulfoxide Cryopreserved Platelets
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