Management of Platelet Transfusion Therapy in Patients With Blood Cancer or Treatment-Induced Thrombocytopenia

Management of Venous Thromboembolic Events (VTE) in Patients With Hematologic Disorders and Treatment-Induced Thrombocytopenia: A Pilot Study

This pilot clinical trial compares the safety of two different platelet transfusion "thresholds" among patients with blood cancer or treatment-induced thrombocytopenia whose condition requires anticoagulant medication (blood thinners) for blood clots. Giving relatively fewer platelet transfusions may reduce the side effects of frequent platelet transfusions without leading to undue bleeding.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Primary Myelofibrosis; Thrombocytopenia; Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Venous Thromboembolism; Myelodysplastic Syndrome; B-Cell Non-Hodgkin Lymphoma; Hematopoietic Cell Transplantation Recipient; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Biphenotypic Leukemia; Secondary Myelofibrosis; Hematologic and Lymphocytic Disorder; T-Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Biological: Platelet Transfusion; Biological: Platelet Transfusion

Detailed Description

PRIMARY OBJECTIVES:

I. To determine feasibility of a randomized controlled trial comparing two different platelet transfusion thresholds (50 x 10^9/L versus [vs] 30 x 10^9/L) in patients with treatment or malignancy-induced thrombocytopenia requiring therapeutic anticoagulation.

SECONDARY OBJECTIVES:

I. Progressive or new venous thromboembolic (VTE).

II. Progressive or new arterial thromboembolism (ATE).

III. Hemorrhagic events (World Health Organization [WHO] grade 2 or greater).

IV. A composite of I, II and III.

V. Major bleeds (WHO grade 3 or 4).

VI. Number of platelet transfusions per patient during the study period.

VII. Platelet transfusion related complications (including transfusion reactions, alloimmunization and volume overload).

VIII. Degree to which platelet target thresholds are achieved.

OUTLINE: Patients are randomized into 1 of 2 groups.

GROUP I (Lower dose): Patients undergo platelet transfusion on all days when the morning platelet count is below the threshold 30 x 10^9/L for up to 30 days or until the platelet count spontaneously recovers to > 50 x 10^9 for 3 consecutive days in the absence of transfusions.

GROUP II (Higher dose): Patients undergo platelet transfusion on all days when the morning platelet count is below the threshold 50 x 10^9/L for up to 30 days or until the platelet count spontaneously recovers to > 50 x 10^9 for 3 consecutive days in the absence of transfusions.

After completion of study, patients are followed up at 30 days.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Any patient with non-acute promyelocytic leukemia (APL) acute leukemia (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], biphenotypic leukemia) undergoing curative intent chemotherapy OR any patient undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for a hematologic disorder (including acute leukemia as above, chronic myelogenous leukemia [CML], chronic lymphocytic leukemia [CLL], myelodysplastic syndrome [MDS], primary or secondary myelofibrosis, hypereosinophilic syndromes, plasma cell disorders, B-cell or T-cell lymphoma)
• Disease may be measurable or non-measurable
• Diagnosis of symptomatic venous thromboembolism requiring therapeutic-dose anticoagulation (unfractionated or low-molecular weight heparin or oral anticoagulants) throughout the period of hematopoietic recovery
• Anticipated platelet count =< 50 x 10^9/L for >= 5 days within 72 hours of enrollment
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Separate episode of VTE or arterial thrombosis within 3 months of enrollment
• Major bleed (WHO grade 3 or 4) within 6 months of enrollment
• Active bleeding (grade 2 or higher) at the time of enrollment
• History of intracranial bleeding at any time
• Disorders of hemostasis including von Willebrand disease, hemophilia, platelet function disorders
• Concomitant use of aspirin or non-steroidal anti-inflammatory drugs
• Evidence of disseminated intravascular anticoagulation (DIC) as determined by the patient's primary provider
• History of alloimmunization (defined as platelet refractoriness with panel reactive antibody [PRA] > 25%) at the time of or prior to enrollment
• Uncontrolled or concurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris
• Psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or able to become pregnant and unwilling to use two forms of birth control during the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group I (lower dose platelet transfusion); Patients undergo platelet transfusion on all days when the morning platelet count is below the threshold 30 x 10^9/L for up to 30 days or until the platelet count spontaneously recovers to > 50 x 10^9 for 3 consecutive days in the absence of transfusions.	Biological: Platelet Transfusion; Undergo lower dose platelet transfusion; Other Names: Blood Platelet Transfusion; Biological: Platelet Transfusion; Undergo higher dose platelet transfusion; Other Names: Blood Platelet Transfusion
EXPERIMENTAL: Group II (higher dose platelet transfusion); Patients undergo platelet transfusion on all days when the morning platelet count is below the threshold 50 x 10^9/L for up to 30 days or until the platelet count spontaneously recovers to > 50 x 10^9 for 3 consecutive days in the absence of transfusions.	Biological: Platelet Transfusion; Undergo lower dose platelet transfusion; Other Names: Blood Platelet Transfusion; Biological: Platelet Transfusion; Undergo higher dose platelet transfusion; Other Names: Blood Platelet Transfusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Eligible Patients Approached for the Study		Up to 1 year
Number of Patients Approached for But Refusing Consent	Reasons for ineligibility will be reported qualitatively in order to inform future studies.	Up to 1 year
Number of Patients Consenting to Enrollment		Up to 1 year
Number of Patients Eligible		Up to 1 year
Number of Patients Screened and Deemed Ineligible	Reasons for ineligibility will be reported qualitatively in order to inform future studies.	Up to 1 year
Number of Patients Successfully Following Protocol	Will evaluate the number of patients successfully following protocol, defined as receiving transfusions 'on protocol' at the end of the study period.	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Hemorrhagic Events (World Health Organization Grade 2 or Greater)	Will evaluate the incidence of hemorrhagic events (World Health Organization grade 2 or greater).	Up to 1 year
Major Bleeds (World Health Organization Grade 3 or 4)	Will evaluate the major bleeds (World Health Organization grade 3 or 4).	Up to 1 year
Number of Platelet Transfusions Per Patient During the Study Period		Up to 1 year
Percent of Days on Which Subjects Are Transfused (or Transfusion Are Not Given)	The frequency with which transfusions are given despite a platelet count above the determined threshold will be documented, as will the frequency with which transfusions are not administered within 24 hours after a platelet count below the determined threshold.	Up to 1 year
Platelet Transfusion Related Complications	Total number of transfusion reactions, patients experiencing alloimmunization and volume overload will be reported.	Up to 1 year
Progressive or New Arterial Thromboembolism	Will evaluate the progression or new arterial thromboembolism by either documented acute electrocardiographic changes compatible with myocardial injury and/or serum biochemical changes diagnostic of myocardial infarction, or documented imaging (computed tomography or magnetic resonance imaging) changes compatible with infarct due to embolism in the presence of a new neurological deficit, or imaging demonstrated intraluminal filling defects in an arterial distribution accompanied by symptoms of acute ischemia (acute onset pain, pallor, loss of pulses or other end-organ damage).	Up to 1 year
Progressive or New Venous Thromboembolic	Will evaluate the progressive or new venous thromboembolic. Will require imaging confirmation, defined as intraluminal filling defect(s) on contrast-enhanced computed tomography or incompressible venous segment(s) on ultrasonography.	Up to 1 year

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David Garcia, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 9, 2017
• Primary Completion (ACTUAL): December 21, 2018
• Study Completion (ACTUAL): December 21, 2018

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: June 20, 2017
• First Posted (ACTUAL): June 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 17, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Myeloproliferative Disorders; Embolism and Thrombosis; Blood Platelet Disorders; Leukemia, Lymphoid; Leukemia, B-Cell; Lymphoma; Lymphoma, B-Cell; Myelodysplastic Syndromes; Primary Myelofibrosis; Leukemia; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Hematologic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Thromboembolism; Venous Thromboembolism; Lymphoma, T-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Thrombocytopenia; Leukemia, Biphenotypic, Acute
• Other Study ID Numbers: 9799 (OTHER: Fred Hutch/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); NCI-2017-00864 (REGISTRY: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No