Outpatient Platelet Transfusions in Myelodysplastic Syndromes and Leukemia: The OPTIMAL Pilot

Leukemia Clinical Trial

— OPTIMAL  

Official title:

Outpatient Platelet Transfusions in Myelodysplastic Syndromes and Leukemia: The OPTIMAL Pilot

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01615146
• Other study ID #: OHREB 2011500
• Status: Terminated
• Phase: N/A
• First received: June 6, 2012
• Last updated: September 1, 2015
• Start date: June 2012
• Est. completion date: June 2015

Study information

• Verified date: September 2015
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

As a result of the underlying disease or its therapy, it is common for patients with blood cancers to have low platelet counts. While platelet transfusions may be beneficial in preventing or treating bleeding symptoms, in circumstances where the risk of bleeding is low they may be unnecessary or even harmful. As a blood product, transfusion of platelets may be associated with infectious or allergic complications, and frequent hospital visits for transfusion may adversely affect quality of life. Additionally, the potentially overuse of platelet products places a burden on health care resources.

The benefit of the current practice of prophylactic platelet transfusions to prevent hemorrhage is unknown. The randomized data that exists is more than 25 years old and not informative given methodological limitations and the changing standards of supportive care. An alternative, therapeutic, strategy involves only administering platelets to control active bleeding.

The standard of practice in inpatients receiving high dose chemotherapy (either for acute leukemia or as part of stem cell transplantation) is prophylactic platelet transfusions. In outpatients not receiving high dose chemotherapy, the risk of bleeding is significantly lower. No randomized trials have examined the optimal platelet transfusion strategy in outpatients with blood cancers undergoing supportive or palliative therapy. Thus the potential benefit of prophylactic transfusions in the outpatient setting is unknown.

The investigators propose to perform a pilot randomized controlled trial to determine if a larger trial is possible. The ultimate goal is to determine if a strategy of therapeutic platelet transfusions is safe and effective in outpatients with blood cancers and low platelet counts.

Description:

Randomization:

A local study nurse will use a web-based randomization system (permuted random blocks of two or four patients) to allocate consenting patients. Medical and research staff and investigators will be blinded to randomization scheme.

Study Duration and Follow-up:

All patients will be assigned to either a therapeutic or prophylactic platelet transfusion for a 6-month period. This period of time will allow us to assess our primary feasibility outcomes of enrollment, compliance with transfusion protocols, and completion of bleeding evaluations and quality of life questionnaires by patients.

Patients in both groups will have their CBC measured at least weekly while on study. More frequent monitoring of the platelet count may be performed at the discretion of the treating physician. The research team will clinically assess patients within 1 week (+/- 3 days) of randomization, and monthly thereafter. Patients will be asked to report any non-cutaneous grade 2 or greater bleeding immediately to their treating physicians and the study team. All the self-assessments of bleeding will be reviewed at each patient visit to ensure that all clinically relevant bleeding episodes have been captured.

Patients whose platelet count recovers to greater than 20 x 109/L for at least six weeks will be taken off the weekly platelet count monitoring as reflects clinical practice. They will continue to be monitored for the duration of the study. If their platelet count falls to 10 x 109/L or below then they will be restarted on the monitoring and previous transfusion protocol.

Data Collection:

Baseline Data - The following clinical and laboratory data will be collected at the time of enrolment: (1) demographic data, (2) diagnosis including date and disease stage, (3) prior chemotherapy, (4) ECOG performance status, (5) comorbidites, (6) previous platelet and red cell transfusions, (7) red cell transfusion history, (8) prior bleeding events, (9) quality of life (EQ5D) (10) routine bloodwork

Transfusions:

All platelet and red cell transfusions will be recorded including date and number of units. For platelet transfusions, the type of platelet product (e.g. apheresis or buffy coat) and ABO compatibility will recorded. Additionally, the indication for all transfusions (prophylactic or to treat bleeding) will be obtained from the attending physician.

Bleeding Assessment:

Participants will be asked to complete a simple bleeding questionnaire on a daily basis which has been previously tested and used in outpatients with thrombocytopenia. Patients will receive a short training session and written material on how to complete the form. A bleeding assessment will be performed at all study follow-up visits (interview, physical exam and review of daily bleeding forms). Bleeding events will be assigned a bleeding grade by the study personnel. A final bleeding grade will be assigned by an adjudication panel of 2 blinded physicians who will independently assign bleeding scores. Any discrepancies in bleeding scores will be resolved by consensus.

Quality of Life:

Quality of life will be measured using the EQ-5D. The EQ-5D is a validated tool for measurement of health-related quality of life there is a precedent for its use in transfusion medicine trials. Quality of life assessments will be performed at baseline and at all subsequent patient visits.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adults 18 years or older with documented MDS (including MDS-subtype, CMML) or AML (as defined by WHO criteria)

2. Severe thrombocytopenia defined as a platelet count of = 10 x 109/L documented on two consecutive samples at least 7 days apart.

3. Receiving outpatient-based supportive or palliative care including palliative cytoreductive, immunomodulatory or hypomethylating therapy, e.g. hydroxyurea or low dose cytarabine, lenalidomide, azacytidine, or decitabine.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.

Exclusion Criteria:

1. High-dose therapy in past 2 months, e.g. AML-type induction or consolidation therapy

2. Thrombocytopenia suspected to be due to immune or peripheral destruction

3. Splenomegaly, palpated at greater than 5 cm below the costal margin or greater than 20 cm on imaging

4. Alloimmune platelet refractoriness

5. Clinically relevant bleed (grade 3 or higher) within the past 3 months

6. Coagulopathy (prothrombin time or activated partial thromboplastin more than 1.5 times the upper limit of normal or fibrinogen less than 2 g/L)

7. Require anticoagulant therapy, e.g. heparin, or antiplatelet therapy, e.g. aspirin

8. Significant renal impairment (Creatinine more than 1.5 times the upper limit of normal)

9. Geographic inaccessibility resulting in the inability to comply with follow-up visits

10. Pregnant or breast-feeding

11. Unwilling or unable to provide informed consent

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Other:
• Platelet Transfusion
Patients allocated to the therapeutic platelet transfusion group will not receive routine prophylactic platelet transfusions. Platelet transfusions will be given to treat documented clinically relevant bleeding defined as WHO bleeding of grade 2 or greater. Patients may be transfused at the discretion of the treating physician. The indication for all platelet transfusions will be recorded by asking the ordering physician. Patients allocated to the prophylactic platelet transfusions will receive a platelet transfusion when the measured platelet count is < 10 x 109/L. Patients may receive additional platelet transfusions at the discretion of the treating physician. The indication for all platelet transfusions will be recorded.

Locations

Country	Name	City	State
Canada	the Ottawa Hospital	Ottawa	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	Canadian Blood Services, Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility	Overall enrollment, off protocol transfusions per each randomized group, total number of platelet transfusions per group and patient compliance with daily self assessment of bleeding will be evaluated.	18 months	No
Secondary	Bleeding events between therapeutic and Prophylactic transfusion groups	Assessments will include: Non-cutaneous Grade 2 bleeding or higher by the World Heath Organization (WHO) bleeding assessment scale 28(Appendix B); Grade 3 bleeding or higher; Time from randomization to first bleeding event of grade 3 of higher; Total number of red cell transfusion per group; Total number of hospital days per group; Number of completed daily bleeding assessments per group; Quality of life; Mortality	6 month follow up period	Yes