Resiliency in Older Adults Undergoing Bone Marrow Transplant (REBOUND)

REBOUND: REsiliency in Older Adults UNDergoing BOne Marrow Transplant - A Pilot Study of Resiliency Measures in Older Patients Undergoing Allogeneic Blood and Marrow Transplant

The objective of this research is to measure certain indicators of resiliency to better understand which participants who are over 60 years old will respond more positively to bone marrow transplant. This research is being done to determine if there are traits that make recipients more likely to bounce back following allogeneic bone marrow transplant (BMT).

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma; Leukemia; Myelodysplastic Syndrome; Acute Myelogenous Leukemia; Non-Hodgkins Lymphoma; Blood Cancer
• Intervention / Treatment: Other: Bone Marrow Transplant (BMT)

Detailed Description

Allogeneic blood and marrow transplantation (alloBMT) is the only potentially curative therapy for many forms of leukemia, lymphoma, and other hematologic malignancies. As with many forms of cancer, many of the most common indications for alloBMT disproportionally affect older people. Although treatments have improved for older adults undergoing therapies for these diseases, the outcomes are variable and there is little biological knowledge to help identify specific factors that would predict why some people do well with treatment and others develop functional and cognitive decline and other adverse health outcomes.

Data specific to patients older than 60 who have undergone alloBMT are sparse even though the 1 year non-relapse mortality rate in patients older than age 50 at Johns Hopkins is 12%. In none of these studies have geriatric assessment measures in domains such as cognition and function been evaluated. Given the low incidence of non-relapse mortality in the investigators' older patients, the investigators have a unique opportunity to study the factors that influence not only mortality but function after hematopoietic stem cell transplantation. The investigators aim to be able to counsel patients more specifically about likely outcomes after transplant.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Philip Imus, MD; Phone Number: 410-955-8839; Email: pimus1@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Undergoing allogeneic bone marrow transplant at Johns Hopkins Hospital, the indication for which is a hematologic malignancy
• Age ≥60 years
• Ability to walk without human assistance
• Enrollment in concomitant clinical research is permitted but not required
• English-speaking
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Unwillingness or inability to return at 6 months after transplantation for repeated evaluation
• Non-English-speaking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Interventional Arm- Bone Marrow Transplant; Study visits will include the performance of assessments prior to the start of conditioning chemotherapy and at 1 month and 6 months post-BMT. Assessments include: Physical function assessments; questionnaires about general health and current health compared to health one year ago; assessments that measure cognition, attention and memory; assessments regarding personality and psychological and social stressors; Physiological measures includingblood tests- 160 mL of blood during evaluations, and 90mL of blood at the day 180 visit.bone marrow aspirate collected during standard of care bone marrow biopsies pre-transplant and at day 180Saliva collections pre-transplantACTH Stimulation TestOral Glucose Tolerance TestHolter Monitor- to record hear rate variabilityMRI pre-transplant and at Day 180 in a subset of 10 subjects

Other: Bone Marrow Transplant (BMT); Bone marrow transplantation will be conducted according to the investigators' institution's standard of care, or else according to research protocol (if applicable).Study visits that include the performance of assessments will occur prior to the start of conditioning chemotherapy and at 1 month and 6 months post-BMT. All dates are +/- 7 days. The initial study visit will take place during standard of care pre-transplant evaluations, which typically span 3-4 days. The post-BMT visits will take place before or after regularly-scheduled BMT follow up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Physical Performance as assessed by Short Physical Performance Battery (SPPB)	5 measured criteria: unintentional weight loss, exhaustion, low energy expenditure, low grip strength, and slowed waking speed. Scores of 3, 4 and 5 are consistent with frailty, scores of 1 and 2 are consistent with pre-frailty status, and a score of 0 is consistent with a robust or resilient status.	Pre-BMT, Day 30 and Day 180 post transplant
Change in ability to perform activities of daily living as assessed by Instrumental Activities of Daily Living questionnaire	questions about ability to perform activities of daily living (IADL). Scored low functioning (0) to high functioning (8).	Pre-BMT, Day 30 and Day 180 post transplant
Change in upper extremity function as assessed by accelerometry	device worn on wrist for a 24hr period that measures physical activity and sedentary activity. Higher scores= more active.	7 consecutive days pre-BMT, at Day 30 and at Day 180
Change in catecholamines levels as assessed in overnight urine collection samples	Changes in catecholamines level will be assessed in overnight urine collection samples. Levels fluctuate. Analysis will use the Johns Hopkins University (JHU) normal reference range for an adult is Metanephrine (normotensive):45-290 μg/24 hours. Metanephrine (hypertensive): 35-460 μg/24 hours .	Pre-BMT, Day 30 and Day 180 post transplant
Change in Frailty as assessed by the Frailty Phenotype instrument	Frailty Phenotype instrument is used to measure participants' walking speed and grip strength, includes questions about exhaustion, physical activity, weight loss. Higher scores indicate better functional state.	Pre-BMT, Day 30 and Day 180 post transplant
Change in Pittsburgh Fatigability Scale for Older Adults score	self-report tool that normalizes activities in terms of intensity and duration (PFS) this has a range of 0-50 with higher scores indicating greater physical fatigability.	Pre-BMT, Day 30 and Day 180 post transplant
Change in Borg Rating of Perceived Exertion Scale score	scale will be used immediately after a slow-paced 5-minute treadmill walk to assess fatigability (RPE). Higher score indicates higher perceived exertion.	Pre-BMT, Day 30 and Day 180 post transplant
Change in medical history and diseases/conditions self reporting	Questionnaire of past medical history as reported by a subject. This questionnaire does not have a score.	Pre-BMT and Day 180 post transplant
Change in health behaviors as assessed by a questionnaire	This assessment is of self determined overall health as reported by a participant, it has no score.	Pre-BMT and Day 180 post transplant
Change in reporting of patients traumas as assessed by the Hospitalizations, Surgeries, and Falls Questionnaire	Questionnaire includes items on hospitalizations, surgeries, and falls. it has no score.	Pre-BMT and Day 180 post transplant
Change in pain reporting as assessed by the Pain Assessment Questionnaire	questions on overall bodily pain intensity/frequency and pain-related function/interference. Higher scores equal more pain.	Pre-BMT and Day 180 post transplant
Change in anxiety reporting as assessed by the anxiety questionnaire	Questions to assess the presence and severity of anxiety; higher scores = more anxiety.	Pre-BMT and Day 180 post transplant
Change in trauma reporting as assessed by the trauma questionnaire	Questions to assess a participants reporting of any past experiences of several kinds of trauma. It has no score.	Pre-BMT and Day 180 post transplant
Change in cognitive function as assessed by Modified Mini-Mental State Examination	measure of global cognitive function (range 0-100). A score of 100 represents total cognitive function according to 3MS.	Pre-BMT, Day 30, Day 56 and Day 180 post transplant
Change in cognitive ability as assessed by the Montreal Cognitive Assessment	measures global cognitive function (MoCA). Scores range between 0 and 30. A score of 26 or over is considered to be normal.	Pre-BMT, Day 30, Day 56 and Day 180 post transplant
Change in cognitive function as assessed by the Digit Symbol Substitution Test (DSST)	participant fill in a series of symbols correctly coded within 90 seconds. The higher the score, the better the participant's performance.	Pre-BMT, Day 30, Day 56 and Day 180 post transplant
Change in ability to cope with life challenges as assessed by the Coping Self-Efficacy Scale	11-point Likert scale measures perceived ability to cope effectively with life. Scale is 0-10 with 10 = best ability to cope and 0 = no ability to cope.	Pre-BMT and Day 180 post transplant
Change in sense of well-being as assessed by the Subscale of Ryff Psychological Well-being Scale	7-item Likert type scale (from strongly disagree to strongly agree) measures sense of direction and perception of purpose. Scale is 0-7 with 7 = best sense of well-being and 0 = no sense of well-being.	Pre-BMT and Day 180 post transplant
Change in perception and satisfaction with life as assessed by the Meaning in Life Questionnaire and Scale	Likert-type scale measuring perception of meaning and satisfaction with life (MLQ) Scale is 0-7 with 7 = best sense that life has meaning and 0 = no sense that life has meaning.	Pre-BMT and Day 180 post transplant
Change in personality as measured by the Ten Item Personality Inventory (TIPI) Scale	7 point Likert-type scale of disagree to agree with various aspects of personality measuring: extraversion, agreeableness, neuroticism, openness, conscientiousness. TIPI scale scoring. Extraversion: 1, 6R; Agreeableness: 2R, 7; Conscientiousness; 3, 8R; Emotional Stability: 4R, 9; Openness to Experiences: 5, 10R. ("R" denotes reverse-scored items)	Pre-BMT and Day 180 post transplant
Change in optimism as assessed by the Life Orientation Scale-Revised	5 point Likert scale, assessing optimism. 0= strongly disagree; 4 = strongly agree. The total score is from 0 to 24; higher scores indicate more optimism.	Pre-BMT and Day 180 post transplant
Change in perceived loneliness as assessed by the Loneliness Scale	Revised University of California, Los Angeles (UCLA) Loneliness Scale. Each question is rated on a 4-point scale: 1 = never; 2 = Rarely; 3 = Sometimes 4 = Always. All items are summed to give a total score. Higher scores indicate more loneliness	Pre-BMT and Day 180 post transplant
Change in perceived socio-economic status as assessed by the US socioeconomic questionnaire	10-rung ladder to assess a participant's perception of participant's status in society. To score this measure, researchers simply note the number of the rung (1-10) on which the respondent placed their "X".	Pre-BMT and Day 180 post transplant
Change in perceived financial strain as assessed by Financial Strain questionnaire	2 item measure evaluating difficulty and anxiety about money. Higher scores equal higher financial strain.	Pre-BMT and Day 180 post transplant
Change in feeling of community inclusion as assessed by the Social Cohesion Questionnaire	Participants rate their community by rate of agreement. Response is Agree a lot, a little, do not agree with 3 statements about their community.	Pre-BMT and Day 180 post transplant
Change in feeling of isolation as assessed by the Social Isolation/Engagement Questionnaire	7-item measure evaluating social isolation, participation and engagement with others. Higher scores= greater sense of isolation.	Pre-BMT and Day 180 post transplant
Change in perceived confidence in spirituality as assessed by the Religion/Spirituality Questionnaire	5-Item measure for use in epidemiological studies regarding spirituality. Score range from 5-27, with higher scores = more sense of spirituality	Pre-BMT and Day 180 post transplant
Change in feelings of depression as assessed by the Patient Health Questionnaire	Measures depressive symptoms in the last 2 weeks (PHQ-8)	Pre-BMT and Day 180 post transplant
Change in perceived childhood trauma as assessed by the Adverse Childhood Events (ACE) Scale	10-item measure to assess childhood abuse and household dysfunction. Response is yes/no. The ACE Scale is scored by summing the number of items for which respondents answered "yes."	Pre-BMT and Day 180 post transplant
Changes in perceived stress as assessed by the Perceived Stress Scale	5-point Likert scale measures the cognitive appraisal and perceptions of stress in life. Higher score= high level of perceived stress.	Pre-BMT and Day 180 post transplant
Change in bone marrow cell ratios as assessed by Bone Marrow Aspirate	aspirate will be collected during standard of care bone marrow biopsies and analyzed using JHU normal reference ranges.	pre-transplant and at Day 180 post-transplant
Change in hemoglobin tests.	160 mL of blood during evaluations, and 90mL of blood at the day 180 visit. Assessment will be documents using Hopkins normal reference ranges	pre-transplant and then at Day 30, Day 56 and Day 180 post-transplant
changes in salivary plasma free cortisol collection	Saliva collected at home by participants at 4 time points during a single 24 hour period. The mean salivary cortisol concentration is 15.5 +/- 0.8 nmol/L (range, 10.2-27.3) at 0800 h and 3.9 +/- 0.2 nmol/L (range, 2.2-4.1) at 2000 h.	single 24 hour period before BMT and at Day 180 post-transplant
Change in cortisol level	This is part of the ACTH Stimulation test to assess the reactivity of hypothalamic-pituitary-adrenal (HPA) axis. Test After the baseline blood draw is taken, 1mcg (low dose) Cosyntropin (synthetic ACTH) will be given intravenously by a research nursing staff followed by serial blood sampling to test for cortisol levels (mcg/dL).	pre-transplant and at Day 180 post-transplant
Changes in interleukin (IL)-6 level	This is part of the ACTH Stimulation test to assess the reactivity of HPA axis. After the baseline blood draw is taken, 1mcg (low dose) Cosyntropin (synthetic ACTH) will be given intravenously by a research nursing staff followed by serial blood sampling to test for IL-6 levels (pg/ml).	pre-transplant and at Day 180 post-transplant
Change in dehydroepiandrosterone (DHEA) level	This is part of the ACTH Stimulation test to assess the reactivity of HPA axis. After the baseline blood draw is taken, 1mcg (low dose) Cosyntropin (synthetic ACTH) will be given intravenously by a research nursing staff followed by serial blood sampling to test for DHEA levels (µg/dL).	pre-transplant and at Day 180 post-transplant
Change in glucose tolerance as assessed by the Oral Glucose Tolerance Test (OGTT)	Participants will fast overnight and then be given the 75 gram glucose oral load followed by blood draws at 0, 30. 60 and 120 minutes. At 120min, below 140mg/dL= normal blood sugar. 200mg/dL or higher= diabetes	pre-transplant and at Day 180 post-transplant
Change in heart rate variability as assessed by the "myPatch" Holter monitor	lightweight digital device that records and stores electrocardiogram (ECG) data on a continuous basis during study visits. A normal resting heart rate for adults ranges from 60 to 100 beats per minute. Generally, a lower heart rate at rest implies more efficient heart function.	During clinic visits at pre-transplant, Day 30, Day 56 and Day 180
Change in attention as assessed by the Flanker Inhibitory Control and Attention Test score	Measures attention and inhibitory control. Scoring is 0-10. Details and interpretations are available in the NIH toolbox scoring and interpretation guide.	pre-transplant, once a week from Day of transplant to Day 60 and at Day 180 post-transplant

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Institutes of Health (NIH); National Institute on Aging (NIA)
• Investigators: Principal Investigator: Philip Imus, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2018
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: December 3, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Resiliency; Allogeneic blood and marrow transplantation (alloBMT); REBOUND; over age 60
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Lymphoma; Myelodysplastic Syndromes; Hematologic Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: J1849; UH2AG056933 (U.S. NIH Grant/Contract); IRB00165139 (Other Identifier: Johns Hopkins School of Medicine)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No