Phase 1 Safety Study of Dimethyl Sulfoxide Cryopreserved Platelets

Phase 1

Completed

Conditions: Thrombocytopenia

Interventions: Biological: CPP
Biological: LSP

Registration Number: NCT02078284

Lead Sponsor: U.S. Army Medical Research and Development Command

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 3 with 2 units of CPP	CPP	A single 30 to 60 minute intravenous (IV) infusion of 2 units of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
Cohort 3 with 1 unit of LSP	LSP	A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP)
Cohort 1 with 1 unit of LSP	LSP	A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP)
Cohort 2 with 1 unit of CPP	CPP	A single 30 to 60 minute intravenous (IV) infusion of 1 unit of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
Cohort 4 with 1 unit of LSP	LSP	A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP
Cohort 4 with 3 units of CPP	CPP	A single 30 to 60 minute intravenous (IV) infusion of 3 units of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
Cohort 1 with 0.5 units of CPP	CPP	A single 30 to 60 minute intravenous (IV) infusion of 0.5 unit of dimethyl sulfoxide (DMSO) cryopreserved platelets (CPP)
Cohort 2 with 1 unit of LSP	LSP	A single 30 to 60 minute intravenous (IV) infusion of 1 unit of liquid stored platelets (LSP)

Primary Outcome Measures

Name	Time	Method
Adverse Events (AEs) by Level of Severity	day of thru 6 days after transfusion	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 With Thrombotic Events	6 days after transfusion	Subjects with any signs or symptoms of thrombotic events.
Number of Subject Who Experienced Adverse Events (AEs) for a Specific Severity	day of thru 6 days after transfusion	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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (4): Puget Sound Blood Center
🇺🇸
Seattle, Washington, United States
Hoxworth Blood Center
🇺🇸
Cincinnati, Ohio, United States
University of Washington, Division of Hematology
🇺🇸
Seattle, Washington, United States
Dartmouth-Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States