Identifying Best Approach in Improving Quality of Life and Survival After a Donor Stem Cell Transplant in Older, Medically Infirm, or Frail Patients With Blood Diseases

Study Overview
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Brief Summary
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This phase II/III trial studies the best approach in improving quality of life and survival after a donor stem cell transplant in older, weak, or frail patients with blood diseases. Patients who have undergone a transplant often experience increases in disease and death. One approach, supportive and palliative care (SPC), focuses on relieving symptoms of stress from serious illness and care through physical, cultural, psychological, social, spiritual, and ethical aspects. While a second approach, clinical management of comorbidities (CMC) focuses on managing multiple diseases, other than cancer, such as heart or lung diseases through physical exercise, strength training, stress reduction, medication management, dietary recommendations, and education. Giving SPC, CMC, or a combination of both may work better in improving quality of life and survival after a donor stem cell transplant compared to standard of care in patients with blood diseases.

Detailed Description
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OUTLINE: Patients are randomized to 1 of 4 arms. ARM I: Patients undergo SPC on days -15 before to +56 after transplant. ARM II: Patients undergo a CMC program on days -15 before to +56 after transplant. ARM III: Patients undergo interventions as outlined in Arm I and Arm II. ARM IV: Patients receive standard of care. In all arms, patients undergo HCT on day 0 and complete questionnaires and surveys at enrollment and 30, 90, 180, and 365 days post HCT. In all arms patients complete a 4-meter walk test, 6-minute walk test, up and go test, measured strength test and cognitive assessment at enrollment, 90, 180, and 365 days post HCT. Patients may also complete surveys on medical and non-medical (transportation, lodging) costs related to transplant after HCT.

Official Title
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Seamless Phase II-Phase III Randomized Clinical Trial to Identify and Confirm the Most Promising Novel Intervention to Alleviate Morbidity and Mortality After Allogeneic Hematopoietic Cell Transplantation Among Older, Medically Infirm, or Frail Patients With Hematological Diseases

Conditions
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Hematopoietic and Lymphoid Cell Neoplasm, Non-Neoplastic Hematologic and Lymphocytic Disorder

Intervention / Treatment
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* Other: Supportive Palliative Care
* Other: Clinical Management
* Other: Best Practice
* Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
* Other: Questionnaire Administration
* Other: Quality-of-Life Assessment
* Other: Survey Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Vulnerable patients as defined by one or more of the following criteria Age 65 years or older Having Hematopoietic Cell Transplantation - Comorbidity Index (HCT-CI) scores of >= 3 (for patients that could be 20 years old and older) Having frailty as determined by walk speed of < 0.8 m/s using 4-meter walk test (for patients 50 years old and older) Patients considered or referred for allogeneic HCT to treat a hematological malignant or non-malignant disease Able to speak and read English - interaction with the interventionist trainer and endpoint measurement must occur in English Willing and able to provide informed consent Planned allogeneic HCT within 3 weeks - all types of donors and all sorts of conditioning regimens are allowed. Patients with suspected active disease (relatively old disease staging or relatively old intervention) or significant comorbidity (e.g. suspicious untreated pulmonary nodules) based on prior evaluations, that could delay the transplant would be considered for enrollment within a tighter window (10-14 days before allogeneic HCT) to allow for completed pre-HCT work-up evaluations that would confirm readiness to proceed with transplant Able to exercise at low to moderate intensity, specifically taking into consideration the rare circumstances where subjects are not able to exercise due to either birth deformity or prior traumatic injury that affects their gait Adequate cardiopulmonary reserve, as judged by data from the patient's electronic medical record as to whether a patient could walk up one flight of stairs, no need for supplemental oxygen, and/or physician judgment Exclusion Criteria: Orthopedic, neurologic or other problems which prevent safe ambulation and protocol adherence. Information on prior falls and other recent orthopedic or neurologic problems will be used to make judgment about protocol eligibility Participation in another intervention clinical trial with HRQOL as a primary endpoint Planned donor lymphocyte infusion (DLI) within 90 days post-transplant Planned anti-cytotoxic therapies, other than tyrosine kinase inhibitors or single-agent monoclonal antibody, or FLT-3 inhibitors within 90 days of post-transplant unless pre-approved by the protocol principal investigator (PI)

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (SPC)<br>Patients undergo SPC on days -15 before to +56 after transplant. Patients undergo HCT on day 0 and complete questionnaires and surveys at enrollment, 30, 90, 180, and 365 days post HCT. Patients complete a 4-meter walk test, 6-minute walk test, up and go test, measured strength test and cognitive assessment at enrollment, 90, 180, and 365 days post HCT. Patients may also complete surveys on medical and non-medical (transportation, lodging) costs related to transplant after HCT. | Other: Supportive Palliative Care<br>* focuses on relieving symptoms of stress from serious illness and care through physical, cultural, psychological, social, spiritual, and ethical aspects<br>* Other names: PA-Palliative Therapy;Procedure: Allogeneic Hematopoietic Stem Cell Transplantation<br>* Undergo HCT<br>* Other names: Stem Cell Transplantation;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Survey Administration<br>* Complete surveys<br>|
| Experimental: Arm II (CMC)<br>Patients undergo a CMC program on days -15 to 56. Patients undergo HCT on day 0 and complete questionnaires and surveys at enrollment, 30, 90, 180, and 365 days post HCT. Patients complete a 4-meter walk test, 6-minute walk test, up and go test, measured strength test and cognitive assessment at enrollment, 90, 180, and 365 days post HCT. Patients may also complete surveys on medical and non-medical (transportation, lodging) costs related to transplant after HCT. | Other: Clinical Management<br>* physical exercise, strength training, stress reduction, medication management, dietary recommendations, and education<br>Procedure: Allogeneic Hematopoietic Stem Cell Transplantation<br>* Undergo HCT<br>* Other names: Stem Cell Transplantation;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Survey Administration<br>* Complete surveys<br>|
| Experimental: Arm III (SPC and CMC)<br>Patients undergo interventions as outlined in Arm I and Arm II. Patients undergo HCT on day 0 and complete questionnaires and surveys at enrollment 30, 90, 180, and 365 days post HCT. Patients complete a 4-meter walk test, 6-minute walk test, up and go test, measured strength test and cognitive assessment at enrollment, 90, 180, and 365 days post HCT. Patients may also complete surveys on medical and non-medical (transportation, lodging) costs related to transplant after HCT. | Other: Supportive Palliative Care<br>* focuses on relieving symptoms of stress from serious illness and care through physical, cultural, psychological, social, spiritual, and ethical aspects<br>* Other names: PA-Palliative Therapy;Other: Clinical Management<br>* physical exercise, strength training, stress reduction, medication management, dietary recommendations, and education<br>Procedure: Allogeneic Hematopoietic Stem Cell Transplantation<br>* Undergo HCT<br>* Other names: Stem Cell Transplantation;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Survey Administration<br>* Complete surveys<br>|
| Active Comparator: Arm IV (standard of care)<br>Patients receive standard of care. Patients undergo HCT on day 0 and complete questionnaires and surveys at enrollment, 30, 90, 180, and 365 days post HCT. Patients complete a 4-meter walk test, 6-minute walk test, up and go test, measured strength test and cognitive assessment at enrollment, 90, 180, and 365 days post HCT. Patients may also complete surveys on medical and non-medical (transportation, lodging) costs related to transplant after HCT. | Other: Best Practice<br>* Given standard of care<br>* Other names: standard therapy;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Survey Administration<br>* Complete surveys<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in health-related quality of life (HRQOL) (Phase II) | The arm with the largest mean change in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) from baseline to day 90. The Wilcoxon rank-sum test will be used to compare change in FACT-BMT between arms, and this will also be the test to be used in computation of the conditional power at the end of phase II. | First 90 days after HCT | 
| Survival after hematopoietic cell transplantation (HCT) (Phase III) |  | At 1 year after HCT | 
| Change in HRQOL (Phase III) | Will be measured by the FACT-BMT. | Baseline to 90 days post-HCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of overall survival | Overall survival will be compared between each of the experimental arms and the usual care only (UCO) arm using the log-rank test. Arms that do not survive the screening phase will also be included for comparison. | Up to 1 year | 
| Non-relapse mortality | Will be compared between arms using appropriate tests for continuous data (two-sample t-test or Wilcoxon rank-sum test, as appropriate for two-group comparisons; analysis of variance (ANOVA) or Kruskal-Wallis test for comparisons involving more than two groups). Will use generalized estimating equations (GEEs) approach for regression models, which can accommodate the within patient correlation structure and arbitrary patterns of missing data and also allow for the population average interpretation. | At 90 days and up to 1 year | 
| Cumulative incidence of relapse | Will be compared between arms using appropriate tests for continuous data (two-sample t-test or Wilcoxon rank-sum test, as appropriate for two-group comparisons; ANOVA or Kruskal-Wallis test for comparisons involving more than two groups). Will use GEEs approach for regression models, which can accommodate the within patient correlation structure and arbitrary patterns of missing data and also allow for the population average interpretation. | Up to 1 year | 
| Relapse-free survival | Will be compared between arms using appropriate tests for continuous data (two-sample t-test or Wilcoxon rank-sum test, as appropriate for two-group comparisons; ANOVA or Kruskal-Wallis test for comparisons involving more than two groups). Will use GEEs approach for regression models, which can accommodate the within patient correlation structure and arbitrary patterns of missing data and also allow for the population average interpretation. | Up to 1 year | 
| Cumulative incidence of frailty | Will be compared between arms using appropriate tests for continuous data (two-sample t-test or Wilcoxon rank-sum test, as appropriate for two-group comparisons; ANOVA or Kruskal-Wallis test for comparisons involving more than two groups). Will use GEEs approach for regression models, which can accommodate the within patient correlation structure and arbitrary patterns of missing data and also allow for the population average interpretation. | Up to 1 year | 
| Cumulative incidence of disability | Will be compared between arms using appropriate tests for continuous data (two-sample t-test or Wilcoxon rank-sum test, as appropriate for two-group comparisons; ANOVA or Kruskal-Wallis test for comparisons involving more than two groups). Will use GEEs approach for regression models, which can accommodate the within patient correlation structure and arbitrary patterns of missing data and also allow for the population average interpretation. | Up to 1 year | 
| Frequency of hospitalization | Will be compared between arms using appropriate tests for continuous data (two-sample t-test or Wilcoxon rank-sum test, as appropriate for two-group comparisons; ANOVA or Kruskal-Wallis test for comparisons involving more than two groups). Will use GEEs approach for regression models, which can accommodate the within patient correlation structure and arbitrary patterns of missing data and also allow for the population average interpretation. | Up to 90 days after HCT | 
| Duration of each hospitalization | Will be compared between arms using appropriate tests for continuous data (two-sample t-test or Wilcoxon rank-sum test, as appropriate for two-group comparisons; ANOVA or Kruskal-Wallis test for comparisons involving more than two groups). Will use GEEs approach for regression models, which can accommodate the within patient correlation structure and arbitrary patterns of missing data and also allow for the population average interpretation. | Up to 90 days after HCT | 
| Number of admissions to intensive care unit | Will be compared between arms using appropriate tests for continuous data (two-sample t-test or Wilcoxon rank-sum test, as appropriate for two-group comparisons; ANOVA or Kruskal-Wallis test for comparisons involving more than two groups). Will use GEEs approach for regression models, which can accommodate the within patient correlation structure and arbitrary patterns of missing data and also allow for the population average interpretation. | Up to 90 days after HCT | 
| Duration of admissions to intensive care unit | Will be compared between arms using appropriate tests for continuous data (two-sample t-test or Wilcoxon rank-sum test, as appropriate for two-group comparisons; ANOVA or Kruskal-Wallis test for comparisons involving more than two groups). Will use GEEs approach for regression models, which can accommodate the within patient correlation structure and arbitrary patterns of missing data and also allow for the population average interpretation. | Up to 90 days after HCT | 
| Days out of hospital alive | Will be compared between arms using appropriate tests for continuous data (two-sample t-test or Wilcoxon rank-sum test, as appropriate for two-group comparisons; ANOVA or Kruskal-Wallis test for comparisons involving more than two groups). Will use GEEs approach for regression models, which can accommodate the within patient correlation structure and arbitrary patterns of missing data and also allow for the population average interpretation. | Up to 90 days after HCT |