Red Cell Transfusion Goals in Patients With Acute Leukemias

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Prospective Randomized Clinical Feasibility Study of Red Cell Transfusion Goals in Patients With Acute Leukemias

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02086773
• Other study ID #: J13126
• Secondary ID: NA_00089706
• Status: Completed
• Phase: Phase 1
• Start date: April 2014
• Est. completion date: September 2015

Study information

• Verified date: January 2019
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study to determine if a lower hemoglobin transfusion threshold, 7 g/dL, has a safety profile similar to that of the current standard transfusion threshold of 8 g/dL.

Description:

Transfusion of red blood cells (RBCs) is vitally important for the care of patients undergoing myelosuppressive therapy for acute leukemia. The therapeutic approach to this disease involves the use of high doses of chemotherapy to treat the blood cancers and bone marrow disorders; but it damages the marrow and blood system. Malignant and healthy stem cells are affected by the chemotherapy, and even when the malignant cells are killed, it can take weeks for the healthy cells to reconstitute the marrow. At diagnosis and before bone marrow recovery post treatment, RBCs are needed to support the patient. Current practices at major comprehensive cancer centers all utilize liberal hemoglobin transfusions triggers of 8-9 g/dL or higher. Higher hemoglobin levels in these high risk patients may have benefits such as better energy and organ function. However, research in a variety of clinical settings, suggests that a higher hemoglobin transfusion threshold is associated with the same or even higher mortality rates compared to lower hemoglobin thresholds (7-8 g/dL). These other settings include prospective randomized trials in high-risk orthopedic surgery patients, critically ill adult and pediatric ICU patients, acute GI bleed patients, and patients undergoing cardiac surgery. One clinical scenario where the ideal transfusion threshold is unknown is in patients receiving chemotherapy for hematologic malignancies. Transfusion requirements and triggers have not been systematically studied in acute leukemia or other cancers. Acute leukemia carries a high mortality; any unnecessary increase in morbidity or mortality is not acceptable. Without a clear benefit of higher transfusion thresholds, the added risks and costs of transfusion may be substantial and unnecessary. The investigators plan to study this issue in this pilot and feasibility study by randomly assigning patients treated for acute leukemia to be transfused with RBCs at either a higher or lower hemoglobin concentration trigger point. In this way, the investigators will be able to accurately determine if there is benefit or harms to having a lower or higher red cell count during the induction treatment and recovery period for patients with acute leukemias. This study will also collect information evaluating the advantages and disadvantages of the two transfusion thresholds and the feasibility of expanding the study to a large randomized trial.This safety data will serve as a platform for a larger mortality study in leukemia and possibly additional studies in solid tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Acute leukemia patients (AML, ALL, APL, treatment-related myeloid neoplasm, high grade MDS)

• Admitted with plans for inpatient myelosuppressive chemotherapy (with standard of care or protocol regimens)

Exclusion Criteria:

• Age less than 18 years

• Acute coronary syndrome as defined by active chest pain, dynamic ECG changes, troponin greater than 2.5

• Active blood loss

• Receiving erythropoietin stimulating agents prior to admission

• Chronic Renal Failure in Renal Replacement Therapy

• Documented wish against transfusion for personal or religious beliefs

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Lymphocytic Leukemia (ALL)
• Acute Myelogenous Leukemia (AML)
• Acute Promyelocytic Leukemia (APL)
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Promyelocytic, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• Red blood cell transfusion

Locations

Country	Name	City	State
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Country where clinical trial is conducted

United States, 

References & Publications (1)

DeZern AE, Williams K, Zahurak M, Hand W, Stephens RS, King KE, Frank SM, Ness PM. Red blood cell transfusion triggers in acute leukemia: a randomized pilot study. Transfusion. 2016 Jul;56(7):1750-7. doi: 10.1111/trf.13658. Epub 2016 May 20. Erratum in: T — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tolerance of low transfusion threshold as assessed by the percentage of participants who crossed over from the low arm to the high arm.		60 days
Secondary	Safety of low vs. high transfusion threshold as assessed by total difference in number of transfusions given per participant	Overall safety is determined by the total difference between arms for the number of transfusions given per participant	60 days
Secondary	Safety of low vs. high transfusion threshold as assessed by number of participants experiencing neutropenic infections	Overall safety is determined by the total difference between arms for number of participants experiencing neutropenic infections, where neutropenia is defined as absolute neutrophil count < 500/mcL.	60 days
Secondary	Safety of low vs. high transfusion threshold as assessed by number of grade 3-4 bleeding events as defined by CTCAE 4.0		60 days
Secondary	Safety of low vs. high transfusion threshold as assessed by number of deaths attributed to induction chemotherapy		60 days
Secondary	Safety of low vs. high transfusion threshold as assessed by number of participants with at least one grade 3-5 non-hematological toxicity by CTCAE 4.0.		60 days
Secondary	Feasibility as determined by percentage of participants consented	As per protocol-defined criteria, the transfusion strategy being tested would be deemed feasible if all of the following criteria are met: 1) More than 50% of eligible patients could be consented; 2) More than 75% of participants randomized to the low arm tolerated the 7 g/dL transfusion threshold; 3) Fewer than 15% of participants crossed over from the low arm to the high arm; 4) The study was not paused for safety concerns.	60 days
Secondary	Feasibility as determined by percentage of participants who tolerate 7g/dL transfusion	As per protocol-defined criteria, the transfusion strategy being tested would be deemed feasible if all of the following criteria are met: 1) More than 50% of eligible patients could be consented; 2) More than 75% of participants randomized to the low arm tolerated the 7 g/dL transfusion threshold; 3) Fewer than 15% of participants crossed over from the low arm to the high arm; 4) The study was not paused for safety concerns.	60 days
Secondary	Feasibility as determined by percentage of participants who crossed over from the low arm to the high arm	As per protocol-defined criteria, the transfusion strategy being tested would be deemed feasible if all of the following criteria are met: 1) More than 50% of eligible patients could be consented; 2) More than 75% of participants randomized to the low arm tolerated the 7 g/dL transfusion threshold; 3) Fewer than 15% of participants crossed over from the low arm to the high arm; 4) The study was not paused for safety concerns.	60 days
Secondary	Number of transfusions	Median number of red cell and platelet transfusions given per participant.	60 days
Secondary	Neutropenic infections	Number of participants in each arm experiencing neutropenic infections, where neutropenia is defined as absolute neutrophil count < 500/mcL.	60 days
Secondary	Bleeding	Number of grade 3-4 bleeding events as defined by CTCAE 4.0.	60 days
Secondary	Length of stay	Median length of inpatient stay in days. This is for the initial inpatient stay for induction chemotherapy only (chemotherapy itself was not part of this protocol).	60 days
Secondary	Treatment-related mortality	Number of deaths attributed to induction chemotherapy.	60 days
Secondary	End organ dysfunction	Number of participants with at least one grade 3-5 nonhematological toxicity as defined by CTCAE 4.0.	60 days
Secondary	Performance status scores	Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status < 2. The ECOG scale is rated from 0 to 5, where 0 is best health and 5 is dead.	60 days
Secondary	Incidence of crossover	Number of participants who crossed over from the low to the high arm due to symptomatic anemia (defined as Hb < 8 g/dL with symptoms).	60 days
Secondary	Cost savings	Estimated per-patient cost savings of the low transfusion threshold compared to the high transfusion threshold.	60 days
Secondary	Fatigue scores	Median difference in fatigue scores as graded on the National Cancer Institute Fatigue Scale. Scores are from 0 to 10, where 0 is no fatigue and 10 is the worst possible fatigue.	60 days