Blood and Lymph Conditions

All Conditions

Anemia

Patients will receive a transfusion under standard care

Patients will not receive an otherwise-indicated red blood cell transfusion

No-Transfuse

Daryl J Kor

Do ambulatory RBC transfusions improve home functional status?

Background: Red blood cell (RBC) transfusion is frequently employed in both ambulatory and hospital environments with the aim of improving patient functional status. The efficacy of this 10.5 billion dollar per year practice however has been increasingly called into question. The Investigators propose to directly measure the impact of outpatient RBC transfusions on at-home functional status by recording several physiological parameters and quantifiable physical activity metrics, e.g. daily energy expenditure and daily total step count, using the ActiGraph wGT3X-BT. This device is an accelerometer-based wearable similar in size to a small watch and is worn at the waist. Study participants will wear the device during the course of their daily activities giving the investigators quantifiable insight into activity levels in the home environment.

Methods/Design: This will be a randomized crossover pilot clinical trial with participant study duration of 28 days. The crossover nature allows each patient to serve as his/her own control. Details of the study design are provided in the text. Briefly, patients presenting at Mayo Clinic Scottsdale's Ambulatory Infusion Center (AIC) will be randomized to one of two arms: 1) receive an RBC transfusion as scheduled (transfuse), or 2) abstain from the scheduled transfusion (no-transfuse). After an appropriate washout period, patients will cross from the transfuse arm to the no-transfuse arm or vice-versa. Activity levels will be recorded continuously throughout the study with no need for intervention by the patient. In addition to device data, survey data will be collected via a weekly telephone interview. The primary outcome measures will include both technical performance metrics such as daily energy expenditure as well as practical performance metrics such as changes in step count. A variety of secondary outcome measures include daily sedentary time and PROMIS Global 10 scores.

Discussion: This trial will directly assess the impact of red blood cell transfusion on patient functional status in the location most important - the home. Patient recruitment will begin in August 2016 and is due to be completed in August 2017.

Red Blood Cell Transfusion in the Ambulatory Setting: Impact on Home Functional Status

Arizona State University

Mayo Clinic

Prinicipal Investigator

Symptoms and General Pathology

Neoplasms

Behaviors and Mental Disorders

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Quality of Life

Central Nervous System Depressants

All Drugs and Chemicals

Other Dietary Supplements

Benzocaine

Tannic Acid

Intervention: Red Blood Cell transfusions. Transfuse pRBC at a higher threshold- maintain Hb level between 110 and 120 g/L: to achieve this, 2 units of pRBCs are transfused when Hb level is \< 105 g/L and 1 unit of RBCs when Hb level is 105-110 g/L.

Transfusions administered more frequently.

Intervention: Red Blood Cell transfusions. Transfuse pRBC at standard of care thresholds- maintain Hb level between 85 and 100 g/L: to achieve this, 2 units of packed red blood cells (pRBCs) will be transfused when the Hb level is \< 80 g/L and 1 unit of pRBCs when Hb level is 80-85 g/L: standard administration

Red Blood Cell Transfusions

Jennifer Gallagher

Geetha Yogendron

Erin Jamula, MSc

Brian Leber, MD

Karen Yee, MD

Rena Buckstein

Rena Buckstein, MD

Myelodysplastic syndromes (MDS) are bone marrow malignancies characterized by poor bone marrow function that may progress to acute myeloid leukemia. Many patients become red blood cell transfusion-dependent. Transfusion dependence is associated with inferior quality of life (QOL). However, the relationship between the degree of anemia and QOL is less clear. A commonly used transfusion strategy is to target the hemoglobin (Hb) in the range of 80-90 g/L (normal hemoglobin \> 120-130g/L). The question is: would a higher hemoglobin target lead to improvement in QOL despite the negative impact transfusion dependence may have on QOL (due to associated time commitments, expense, transfusion reactions etc). Several groups have prospectively shown that targeting hemoglobin levels of greater than 120 g/L (with hematopoietic growth factors (HGFs) and/or blood transfusions) or incremental increases of 15-20 g/L (with HGFs alone) were associated with improved QOL. The investigators MDS program has been conducting prospective assessments of QOL since 2007 in all registered and consented patients using a variety of validated questionnaires. Preliminary analysis (in 236 patients) revealed that, compared with an age-matched healthy general population, MDS patients have inferior QOL. Transfusion dependence and anemia were independently predictive of poor functioning, fatigue and decreased health utility. Furthermore, a hemoglobin level of ≥100 g/L seemed to be the key threshold for improvement in function and symptom scores. The investigators hypothesize that the target hemoglobins in transfusion dependent MDS patients are too low and this may account for their inferior quality of life. Our goal is to compare the effect on QOL of a restrictive strategy (which is the current standard of care), with a liberal transfusion strategy in a large randomized controlled trial of transfusion dependent MDS outpatients. Before embarking on such an endeavor, the investigators must first prove feasibility in a smaller pilot randomized controlled trial.

Red Blood Cell Transfusion Thresholds and QOL in MDS

Red Blood Cell Transfusion Thresholds and QOL in MDS (EnhanceRBC): a Pilot, Feasibility Study

The percentage compliance of q2weekly hemoglobins being within or above the target range of the RBC transfusion threshold assigned (after the 4 week run-in at study start as defined above). We will consider this study feasible and worthy of future development into a larger randomized trial (powered for QOL difference) if compliance is ≥70%. A compliance rate of 50-70%, would not exclude going forward with such an RCT but only after careful discussion and statistical planning

* Number of patients ineligible due to screen failure
* Enrolment rates defined by the number of enrolled patients/month
* Percentage compliance with QOL questionnaire completion at least 3 serial times
* Other logistical issues related to protocol implementation, recruitment rates, randomization implementation strategy, data collection, patient tolerability of study schedule

• The magnitude of change in physical functioning, fatigue, dyspnea and global health scores on the EORTC QLQ-C30, calculated health utility on the EQ-5D and fatigue score on FACT-F comparing the 2 RBC transfusion thresholds above.

* The rate of transfusion reactions (as defined by TTISS (Transfusion Transmitted Injuries Surveillance System by Public Health Agency of Canada))
* Rate of adverse events such as cardiac events and thromboembolic events as per NCI CTCAE version 4.0 criteria

Rate of alloimmunization to significant blood group antigens

• The impact on transfusion associated hemosiderosis rates and burdens (as measured by changes in ferritin levels and iron chelating medications)

How many units of blood are required to maintain the hemoglobin threshold chosen

• The overall time commitment per group, measured as the time spent in transfusion medicine clinic

Princess Margaret Hospital, Canada

Juravinski Cancer Center

Sunnybrook Health Sciences Centre

Cytopenia

Hematinics

Antineoplastic Agents

Epoetin Alfa

Panobinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.

During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.

LBH589 was supplied at dose strengths of 5 mg or 20 mg hard gelatin capsules.

LBH589

Epoetin alfa was supplied as 10000 IU/1 mL in a ready-to-use syringe.

Novartis Pharmaceuticals

This study assessed the efficacy and safety of LBH589 as single agent and in combination with ESA in red blood cell transfusion-dependent Low and Int-1 MDS patients being either refractory to ESA or with a low probability of response. The study had a non-randomized core phase followed by a randomized phase.

LBH589 Alone or in Combination With Erythropoietin Stimulating Agents (ESA) in Patients With Low or Int-1 Risk Myelodysplastic Syndromes (MDS)

A One Year, Open Label, Multicenter Trial of LBH589 Alone or in Combination With ESA in Red Blood Cell Transfusion-dependent LOW and INT-1 MDS Patients Being Either Refractory to ESA or With a Low Probability of Response - the GErman PAnobinostat Low Risk MDS Trial - GEPARD Study

HI-E was assessed according to the modified international working group (IWG) criteria for HI. Erythroid response (pretreatment, \<11 g/dL): Hgb increase by ≥ 1.5 g/dL, relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk, and only RBC transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response evaluation; Platelet response (pretreatment, \< 100 x 109/L): absolute increase of ≥ 30 x 109/L for participants starting with \> 20 x 109/L and platelets Increase from \< 20 x 109/L to \> 20 x 109/L and by at least 100%; Neutrophil response (pretreatment, \< 1.0 x 109/L): at least 100% increase and an absolute increase \> 0.5 x 109/L; Progression or relapse after HI: At least 1 of the following: At least 50% decrement from maximum response levels in granulocytes or platelets, reduction in Hgb by ≥1.5 g/dL, or transfusion dependence.

Objective response (complete remission (CR) + partial remission (PR) and HI-platelet (HI-P) response + HI-neutrophil (HI-N) response) was assessed according to the modified IWG criteria: CR bone marrow with 5% myeloblasts with normal maturation of al cell lines (persistent dysplasia is noted) and peripheral blood with Hgb \>= 11 g/dL platelets \>=100 X 10\^9/L, neutrophils \>= 1.0 x 10\^9/L and blasts 0%. PR = All CR if abnormal before treatment except bone marrow blasts decreased by\>=50% over pretreatment but still \>5% (ellularity and morphology not relevant). HI-P (pretreatment, \< 100 x 109/L) = absolute increase of ≥ 30 x 109/L for participants starting with \> 20 x 109/L and platelets Increase from \< 20 x 109/L to \> 20 x 109/L and by at least 100%; HI-N (pretreatment, \< 1.0 x 109/L) = at least 100% increase and an absolute increase \> 0.5 x 10\^9/L.

The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast \<5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex \>= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high \>=2.5 points (6 months of median survival).

OS was defined as the time from start of treatment to death from any cause.

Time to response was defined as the time from start of treatment to the first documented response (complete \[CR\] or partial \[PR\]) according to modified IWG criteria for HI.

EFS was defined as the time from start of treatment to failure or death from any cause.

PFS was defined as the time from start of treatment to disease progression or death from MDS.

DFS was defined as the time from start of treatment to the time to relapse.

Time to cause-specific death was defined as the time from start of treatment to death related to MDS.

LBH589 - Core Phase

LBH589 - Randomized Phase

LBH589 + ESA - Randomized Phase

Participant, who was eligible for randomization, was not randomized. The participant had stable disease and should have been randomized, but in error, was considered a responder and therefore continued on single agent LBH589.

Not Randomized

Age, Continuous

Sex: Female, Male

Study Director

Participants from the core phase, who had valid response data, were analyzed.

Percentage of Participants With Hematological Response of the Erythropoetic System (HI-E) - Core Phase

32 weeks (n=5,1,1)

52 weeks (n=4,3,1)

LBH589 + Epoetin Alfa

Participants from the randomized phase, who had valid response data, were analyzed.

Percentage of Participants With HI-E - Randomized Phase

Participants from the core phase, who had valid data, were analyzed.

Percentage of Participants With Objective Response During Core Phase

Week 32 ( n=5,1,1)

Week 48 (n=6,5,1)

Participants from the randomized phase, who had valid data, were analyzed.

Percentage of Participants With Objective Response During the Randomized Phase

Baseline (core phase), Low

Baseline (core phase),, INT-1

Baseline (core phase),, INT-2

Baseline (core phase), High

All participants from the core phase were analyzed.

Frequency Distribution of IPSS Score Status - Core Phase

Week 52 (randomized phase), Low

Week 52 (randomized phase), , INT-1

Week 52 (randomized phase), INT-2

Week 52 (randomized phase), HIgh

Only participants from the randomized phase, who had values at week 52, were included in the analysis.

Frequency Distribution of IPSS Score Status - Randomized Phase

Mean Single Scoring Values of the IPSS - Core Phase

Participants from the randomized phase, who had values at week 52, were included in the analysis.

Mean Single Scoring Values of the IPSS - Randomized Phase

Overall Survival (OS) - Overall Period

Time to response could not be evaluated because there was no response.

Time to Response - Overall Period

Event-free survival could not be evaluated because there was no response, no progression or no disease-free period.

Event-free Survival (EFS) - Overall Period

PFS could not be evaluated because there was no progression.

Progression-free Survival (PFS) - Overall Period

DFS could not be evaluated because there was no disease-free period.

Disease-free Survival (DFS) - Overall Period

Time to cause-specific death could not be evaluated because there was no cause-specific death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Red Blood Cell Transfusion in the Ambulatory Setting: Impact on Home Functional Status	NCT02835937	Red Blood Cell ... Anemia Hematology Oncology Ambulatory Care	No-Transfuse	18 Years -	Mayo Clinic
Red Blood Cell Transfusion Thresholds and QOL in MDS	NCT02099669	Myelodysplastic... Quality of Life Red Blood Cell ...	Red Blood Cell ...	18 Years -	Sunnybrook Health Sciences Centre
LBH589 Alone or in Combination With Erythropoietin Stimulating Agents (ESA) in Patients With Low or Int-1 Risk Myelodysplastic Syndromes (MDS)	NCT01034657	Myelodysplastic...	LBH589 Epoetin Alfa	18 Years -	Novartis
LBH589 Alone or in Combination With Erythropoietin Stimulating Agents (ESA) in Patients With Low or Int-1 Risk Myelodysplastic Syndromes (MDS)	NCT01034657	Myelodysplastic...	LBH589 Epoetin Alfa	18 Years -	Novartis

Spots Global Cancer Trial Database for red blood cell transfusions