Acute Biphenotypic Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, B-Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Hematologic and Lymphocytic Disorder, Hematopoietic Cell Transplantation Recipient, Myelodysplastic Syndrome, Primary Myelofibrosis, Secondary Myelofibrosis, T-Cell Non-Hodgkin Lymphoma, Thrombocytopenia, Venous Thromboembolism
Conditions
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.
Interventions
BIOLOGICALPlatelet Transfusion
Undergo lower dose platelet transfusion
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 Consenting to Enrollment | Up to 1 year | — |
| Number of Patients Eligible | Up to 1 year | — |
| 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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). |
| 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. |
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Platelet Transfusion: Undergo lower dose platelet transfusion | 2 |
| 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.
Platelet Transfusion: Undergo higher dose platelet transfusion | 2 |
| Total | 4 |
Baseline characteristics
| Characteristic | Group I (Lower Dose Platelet Transfusion) | Total | Group II (Higher Dose Platelet Transfusion) |
|---|---|---|---|
| Age, Continuous | 42 years | 39 years | 35 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 2 participants | 4 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 1 / 2 | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 |
Outcome results
Primary
Number of Eligible Patients Approached for the Study
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Approached Patients | Number of Eligible Patients Approached for the Study | 4 Participants |
Primary
Number of Patients Approached for But Refusing Consent
Reasons for ineligibility will be reported qualitatively in order to inform future studies.
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Approached Patients | Number of Patients Approached for But Refusing Consent | 0 Participants |
Primary
Number of Patients Consenting to Enrollment
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Approached Patients | Number of Patients Consenting to Enrollment | 4 Participants |
Primary
Number of Patients Eligible
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Approached Patients | Number of Patients Eligible | 4 Participants |
Primary
Number of Patients Screened and Deemed Ineligible
Reasons for ineligibility will be reported qualitatively in order to inform future studies.
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Approached Patients | Number of Patients Screened and Deemed Ineligible | 3 Participants |
Primary
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.
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Approached Patients | Number of Patients Successfully Following Protocol | 2 Participants |
| Group II (Higher Dose Platelet Transfusion) | Number of Patients Successfully Following Protocol | 2 Participants |
Secondary
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).
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Approached Patients | Incidence of Hemorrhagic Events (World Health Organization Grade 2 or Greater) | 0 Participants |
| Group II (Higher Dose Platelet Transfusion) | Incidence of Hemorrhagic Events (World Health Organization Grade 2 or Greater) | 0 Participants |
Secondary
Major Bleeds (World Health Organization Grade 3 or 4)
Will evaluate the major bleeds (World Health Organization grade 3 or 4).
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Approached Patients | Major Bleeds (World Health Organization Grade 3 or 4) | 0 Participants |
| Group II (Higher Dose Platelet Transfusion) | Major Bleeds (World Health Organization Grade 3 or 4) | 0 Participants |
Secondary
Number of Platelet Transfusions Per Patient During the Study Period
Time frame: Up to 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Approached Patients | Number of Platelet Transfusions Per Patient During the Study Period | 2 platelet transfusions |
| Group II (Higher Dose Platelet Transfusion) | Number of Platelet Transfusions Per Patient During the Study Period | 9 platelet transfusions |
Secondary
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.
Time frame: Up to 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Approached Patients | Percent of Days on Which Subjects Are Transfused (or Transfusion Are Not Given) | 0 percentage of study days |
| Group II (Higher Dose Platelet Transfusion) | Percent of Days on Which Subjects Are Transfused (or Transfusion Are Not Given) | 3.8 percentage of study days |
Secondary
Platelet Transfusion Related Complications
Total number of transfusion reactions, patients experiencing alloimmunization and volume overload will be reported.
Time frame: Up to 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Approached Patients | Platelet Transfusion Related Complications | 0 Platelet transfusion complication |
| Group II (Higher Dose Platelet Transfusion) | Platelet Transfusion Related Complications | 2 Platelet transfusion complication |
Secondary
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).
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Approached Patients | Progressive or New Arterial Thromboembolism | 0 Participants |
| Group II (Higher Dose Platelet Transfusion) | Progressive or New Arterial Thromboembolism | 0 Participants |
Secondary
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.
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Approached Patients | Progressive or New Venous Thromboembolic | 0 Participants |
| Group II (Higher Dose Platelet Transfusion) | Progressive or New Venous Thromboembolic | 0 Participants |