Clinical trial NCT02086773: Red Cell Transfusion Goals in Patients With Acute Leukemias
Official title: Prospective Randomized Clinical Feasibility Study of Red Cell Transfusion Goals in Patients With Acute Leukemias
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia
Acute Lymphocytic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Acute Promyelocytic Leukemia (APL)
Keywords: Acute Leukemia
Red Cell Transfusion
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
First posted: 2014-03-13
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Tolerance of low transfusion threshold as assessed by the percentage of participants who crossed over from the low arm to the high arm.
timeFrame: 60 days
Secondary outcomes:
measure: Safety of low vs. high transfusion threshold as assessed by total difference in number of transfusions given per participant
timeFrame: 60 days
measure: Safety of low vs. high transfusion threshold as assessed by number of participants experiencing neutropenic infections
timeFrame: 60 days
measure: Safety of low vs. high transfusion threshold as assessed by number of grade 3-4 bleeding events as defined by CTCAE 4.0
timeFrame: 60 days
measure: Safety of low vs. high transfusion threshold as assessed by number of deaths attributed to induction chemotherapy
timeFrame: 60 days
measure: 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.
timeFrame: 60 days
measure: Feasibility as determined by percentage of participants consented
timeFrame: 60 days
measure: Feasibility as determined by percentage of participants who tolerate 7g/dL transfusion
timeFrame: 60 days
measure: Feasibility as determined by percentage of participants who crossed over from the low arm to the high arm
timeFrame: 60 days
measure: Number of transfusions
timeFrame: 60 days
measure: Neutropenic infections
timeFrame: 60 days
measure: Bleeding
timeFrame: 60 days
measure: Length of stay
timeFrame: 60 days
measure: Treatment-related mortality
timeFrame: 60 days
measure: End organ dysfunction
timeFrame: 60 days
measure: Performance status scores
timeFrame: 60 days
measure: Incidence of crossover
timeFrame: 60 days
measure: Cost savings
timeFrame: 60 days
measure: Fatigue scores
timeFrame: 60 days
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Amy DeZern, MD, MHS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Carson JL, Stanworth SJ, Dennis JA, Trivella M, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021 Dec 21;12(12):CD002042. doi: 10.1002/14651858.CD002042.pub5.