Low accrual rate, strategic reasons

This study evaluates the use of tranexamic acid (TXA) in addition to standard therapy in children receiving chemotherapy or blood and/or marrow transplantation to decrease the risk of bleeding. Half of participants will receive tranexamic acid and half of participants will receive placebo.

The purpose of this study is to conduct a prospective, randomized, blinded, placebo controlled trial to evaluate the safety and feasibility of the addition of antifibrinolytic therapy with tranexamic acid to the standard care in patients who are thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy and/or radiation therapy in order to prevent bleeding. The results of this study will change practice by providing evidence as to whether or not TXA is effective and safe treatment when used as an adjunct to platelet transfusion therapy in the thrombocytopenic patient.

Inclusion Criteria:

• Patients must have a confirmed diagnosis of hematologic malignancy or solid tumor malignancy
• Patients must be undergoing or planned chemotherapy or BMT
• Patients will only be eligible to receive study drug or placebo during inpatient periods
• Patients must be predicted to have thrombocytopenia ≤20,000/microliter (uL) for ≥5 days
• Patient must have a platelet transfusion threshold of ≤30,000/uL
• Patients must be >14 days beyond their last dose of Pegylated(PEG)-Asparaginase or >72 hours beyond their last dose of Erwinia Asparaginase
• Patients must be able to comply with treatment and monitoring

Exclusion Criteria:

• Diagnosis of acute promyelocytic leukemia (APL)
• History of Immune Thrombocytopenic Purpura (ITP), Thrombotic Thrombocytopenic Purpura (TTP) or Hemolytic Uremic Syndrome (HUS)
• Diagnosis of Disseminated Intravascular Coagulopathy (DIC)
• History of inherited or acquired bleeding disorder AND/OR inherited or acquired prothrombotic disorder
• Patient must not have WHO Grade 2 bleeding or greater within 48 hours prior to enrollment or study drug activation
• Patient must not have received PEG-Asparaginase within the 7 day period prior to enrollment. If given within the 8-14 day period prior to enrollment patients are eligible if prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR) and fibrinogen are obtained and are within 1.5 times the upper limits of normal.
• Patient must not be receiving tranexamic acid or other anti-fibrinolytic agent or any other agent to promote hemostasis (which includes DDAVP, recombinant Factor VII, Prothrombin Complex Concentrate, Estrogen Derivatives and Progestins)
• Patient must not be receiving therapy with anticoagulation or antiplatelet therapy (which includes heparin infusion, enoxaparin, aspirin. If anticoagulant/antiplatelet therapy is discontinued when platelet count is <50,000/uL patient will be eligible for enrollment)
• Patient must not be receiving platelet growth factors
• Current thromboembolic event
• History of thromboembolic event <6 months prior to enrollment
• Current/prior history of sinusoidal obstruction disease
• Visible hematuria
• Renal dysfunction (as defined by age-specific creatinine values calculated by Schwartz equation) or hemodialysis or anuria (defined as <10 mL urine/hour over 24 hours)
• History of seizures
• Allergy to tranexamic acid
• Pregnancy
• Unwilling to accept blood product transfusions

Anonymized public data set will be available after publication of primary results

Beginning within 1 year and ending 5 years after trial completion

Researchers who provide a methodologically sound proposal may request data. Proposals should be directed to meghan.mccormick3@chp.edu. To gain access data requestors will need to sign a data access agreement.

From the time of activation of the study drug up to and including 30 days after the last dose of the study drug, an average of 41 days

The pre-specified analysis described in the study protocol stated the following: "For secondary endpoints, events of WHO Grade 2 or higher bleeding will be compared through the use of odds ratio or T-test statistic of means. The mean number of platelet transfusions will be analyzed using a T-test statistic of means." This analysis was not completed as it would be scientifically inappropriate due to insufficient enrollment. Instead a descriptive analysis was completed.

The investigational pharmacy will be notified when patients enroll on trial. When participants meet criteria for randomization, this will be completed by the Investigational Pharmacy. The pharmacy will prepare and distribute to floor nursing staff all doses of tranexamic acid (available in IV form as a colorless liquid) or placebo (as an equal volume of normal saline). Labels will not carry identifiers of which study arm the enrolled patient is on.