PRevention Of BLeeding in hEmatological Malignancies With Antifibrinolytic (Epsilon Aminocaproic Acid)

NCT02074436 | Terminated Phase 2 Results DMC

• 2 other identifiers: IRB00066504Winship2429-13
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Hematological Malignancies; Thrombocytopenia

Keywords

hematological malignancies; thrombocytopenia; aminocaproic acid

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Develop Major Bleeding Episodes

  The primary objective of this study is to compare the percentage of patients who develop major bleeding episodes (WHO grades 3-4) in the group randomized to receive prophylactic EACA versus standard of care prophylactic platelet transfusions. Grade 3 bleeding is defined as a bleed that significantly limits the patient's ability to perform routine activities despite symptomatic therapy and leads to reduction of the dose or discontinuation of the study drug. Grade 4 bleeding is a life-threatening bleed that requires discontinuation of the study drug and the patient is at immediate risk of death

  6 months

Study Arms (2)

Prophylactic EACA

EXPERIMENTAL

Prophylactic EACA 1000 mg PO twice daily if platelets \< 20 x 10⁹/L

Drug: EACA

Platelet transfusion

ACTIVE COMPARATOR

Platelet transfusion if platelet count is \< 20 x 10⁹/L in the outpatient or \< 10 x 10⁹/L in the inpatient setting

Other: Platelet transfusion

Interventions

EACA DRUG

EACA 1000 mg twice a day. Patients will receive platelet transfusion in case of grade ≥ 2 bleeding.

Also known as: Amicar, Aminocaproic acid

Prophylactic EACA

Platelet transfusion OTHER

Prophylactic platelet transfusion. Additional platelet transfusions will be administered in case of grade ≥ 2 bleeding.

Platelet transfusion

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (2)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Atlanta VA Medical Center

Decatur, Georgia, 30033, United States

Location

Related Publications (3)

• Heddle NM, Cook RJ, Sigouin C, Slichter SJ, Murphy M, Rebulla P; BEST Collaborative (Biomedical Excellence for Safer Transfusion). A descriptive analysis of international transfusion practice and bleeding outcomes in patients with acute leukemia. Transfusion. 2006 Jun;46(6):903-11. doi: 10.1111/j.1537-2995.2006.00822.x.

  PMID: 16734806 BACKGROUND

• 2. Gernsheimer, TB Platelet transfusion in the 21st century, ISBT 2011;6: 245-248

  BACKGROUND

• Rebulla P, Finazzi G, Marangoni F, Avvisati G, Gugliotta L, Tognoni G, Barbui T, Mandelli F, Sirchia G. The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. N Engl J Med. 1997 Dec 25;337(26):1870-5. doi: 10.1056/NEJM199712253372602.

  PMID: 9407153 BACKGROUND

MeSH Terms

Conditions

Hematologic Neoplasms; Thrombocytopenia

Interventions

Aminocaproic Acid; Platelet Transfusion

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Platelet Disorders; Cytopenia

Intervention Hierarchy (Ancestors)

Aminocaproates; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Blood Component Transfusion; Blood Transfusion; Biological Therapy; Therapeutics

Limitations and Caveats

Early termination of the study because of recruitment difficulties lead to insufficient data collection and analysis of primary and secondary outcome measures.

Results Point of Contact

• Title: Dr. Ana Antun
• Organization: Emory University

ana.antun@emoryhealthcare.org

404-778-1900

Study Officials

• Ana G. Antun, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 26, 2014
• First Posted: February 28, 2014
• Study Start: May 23, 2014
• Primary Completion: November 24, 2020
• Study Completion: May 14, 2021
• Last Updated: July 19, 2022
• Results First Posted: July 19, 2022

Record last verified: 2022-06

Locations

US (2)