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

Phase 2

Terminated

Conditions: Hematopoietic Cell Transplantation Recipient
Secondary Myelofibrosis
T-Cell Non-Hodgkin Lymphoma
Acute Biphenotypic Leukemia
Acute Myeloid Leukemia
Chronic Lymphocytic Leukemia
Hematologic and Lymphocytic Disorder
Venous Thromboembolism
Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Myelodysplastic Syndrome

Interventions: Biological: Platelet Transfusion

Registration Number: NCT03195010

Lead Sponsor: Fred Hutchinson Cancer Center

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group I (lower dose platelet transfusion)	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.
Group II (higher dose platelet transfusion)	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of Platelet Transfusions Per Patient During the Study Period	Up to 1 year
Platelet Transfusion Related Complications	Up to 1 year	Total number of transfusion reactions, patients experiencing alloimmunization and volume overload will be reported.
Percent of Days on Which Subjects Are Transfused (or Transfusion Are Not Given)	Up to 1 year	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.
Progressive or New Arterial Thromboembolism	Up to 1 year	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).
Progressive or New Venous Thromboembolic	Up to 1 year	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.
Incidence of Hemorrhagic Events (World Health Organization Grade 2 or Greater)	Up to 1 year	Will evaluate the incidence of hemorrhagic events (World Health Organization grade 2 or greater).
Major Bleeds (World Health Organization Grade 3 or 4)	Up to 1 year	Will evaluate the major bleeds (World Health Organization grade 3 or 4).