A Pediatric Trial Using Tranexamic Acid in Thrombocytopenia

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 ≤10,000/uL (for hematologic or
solid tumor malignancies who are not undergoing BMT) or ≤20,000/uL (for patients with
hematologic or solid tumor malignancies who are undergoing BMT)

- Patients must be >14 days beyond their last dose of Pegylated(PEG)-Asparaginase or
Erwinia

- 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 or Erwinia Asparaginase within the 7
day period prior to enrollment. If one of these products is 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/prior history of thromboembolic event

- 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