PRevention Of BLeeding in hEmatological Malignancies With Antifibrinolytic (Epsilon Aminocaproic Acid)
Condition: Hematological Malignancies; Thrombocytopenia
MeSH terms: Neoplasms; Hematologic Neoplasms; Thrombocytopenia
Intervention: EACA; Platelet transfusion
Intervention description: EACA 1000 mg twice a day. Patients will receive platelet transfusion in case of grade ≥ 2 bleeding.; Prophylactic platelet transfusion. Additional platelet transfusions will be administered in case of grade ≥ 2 bleeding.
Intervention MeSH terms: Aminocaproic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No
Keywords: hematological malignancies; thrombocytopenia; aminocaproic acid

Summary:

      STUDY BACKGROUND AND PURPOSE:

      Patients with hematological malignancies (blood-related cancers) often develop
      thrombocytopenia (low platelet count), which can be made worse by cancer treatment.

      Preventive (prophylactic) platelet transfusion remains the standard of care for
      thrombocytopenic patients. However, bleeding remains a significant problem in these patients,
      affecting approximately 20% of patients with acute myeloid leukemia and 34-58% of
      hematopoietic stem cell transplant recipients. Platelet transfusion refractoriness, the
      repeated failure to obtain satisfactory response to platelet transfusions, is a common
      problem. Alternatives to platelet transfusions are desperately needed for these patients.

      Epsilon aminocaproic acid (EACA) blocks a process called fibrinolysis that is an essential
      step in the bleeding process. EACA is approved by the FDA for the treatment of severe
      bleeding-related diseases and complications. A small study has shown EACA to be well
      tolerated and associated with low risk of bleeding in patients with hematological
      malignancies.

      This study will compare EACA versus standard prophylactic platelet transfusion for the
      prevention of bleeding in thrombocytopenic patients with hematological malignancies.

      STUDY DESCRIPTION:

      This is Phase II study to compare EACA versus standard prophylactic platelet transfusion to
      prevent bleeding in thrombocytopenic patients with hematological malignancies. Patients who
      are eligible to take part must give their written agreement before they can be enrolled.

      The study will enroll 100 patients who will be assigned randomly to take EACA twice daily or
      to undergo standard prophylactic platelet transfusion. Patients will be followed for any
      bleeding events, need for platelet transfusion, and any side effects experienced. Patients
      will complete questionnaires to assess their quality of life while on the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age > 18 with a hematological malignancy

          -  Informed consent

          -  Thrombocytopenia with untransfused platelet counts < 20 x 10⁹/L in the out-patient or
             in the in-patient setting and one of the following criteria:

               -  Acute thrombocytopenia in patients with hematological malignancies who are in
                  remission and are receiving myelosuppressive consolidation chemotherapy that is
                  expected to induce marrow aplasia for at least 2 weeks; or

               -  Acute or chronic thrombocytopenia in patients with acute leukemia (myeloblastic
                  or lymphoblastic) receiving induction or re-induction chemotherapy that is
                  expected to induce marrow aplasia for at least 2 weeks; or

               -  Expected chronic thrombocytopenia in patients with newly diagnosed marrow failure
                  syndromes, myelodysplastic syndromes, aplastic anemia, chronic myelomonocytic
                  leukemia or myelofibrosis; or

               -  Expected chronic thrombocytopenia in patients with relapsed or refractory
                  hematological malignancies; or

               -  Hematopoietic stem cell transplant recipients with chronic thrombocytopenia due
                  to chronic graft-versus-host disease (GVHD) or other causes

        Exclusion Criteria:

          -  Acute promyelocytic leukemia

          -  Patient receiving anticoagulation

          -  Patient receiving antiplatelet agents

          -  Patient treated with antifibrinolytic agents (including EACA) within 14 days prior to
             screening

          -  Subjects receiving procoagulant agent including DDAVP, recombinant factor VII or
             prothrombin complex concentrate within 24 hours of enrollment

          -  Subject with known congenital bleeding disorders or platelet dysfunction

          -  Disseminated intravascular coagulation

          -  Fibrinogen level < 150 mg/dl

          -  Patients with known lupus anticoagulant or positive antiphospholipid antibody

          -  History of arterial or venous thromboembolic disease 6 months prior to screening

          -  Patient requiring platelet transfusion threshold of > 20 x 10⁹/L

          -  Active grade ≥ 2 bleeding at the time of randomization, including hematuria

          -  History of grade 4 bleeding

          -  Hematopoietic stem cell transplant recipient within 100 days post-transplant

          -  Pregnancy

          -  Known allergy to EACA

          -  History of veno-occlusive disease of the liver

          -  Myocardial infarction 6 months prior to screening

          -  Unstable angina

          -  Grade 2 renal dysfunction: creatinine > 2-3 times the upper limit of normal