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

Hematopoietic and Lymphoid Cell Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03870750
• Other study ID #: RG1004746
• Secondary ID: NCI-2019-0109798
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: August 15, 2019
• Est. completion date: June 30, 2025

Study information

• Verified date: January 2024
• Source: Fred Hutchinson Cancer Center
• Contact: Mohamed Sorror, MD, MSc
• Phone: 206-667-6298
• Email: msorror[@]fredhutch.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 620
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Hematologic Diseases
• Hematopoietic and Lymphoid Cell Neoplasm
• Non-Neoplastic Hematologic and Lymphocytic Disorder

Intervention

Other:
• Supportive Palliative Care
focuses on relieving symptoms of stress from serious illness and care through physical, cultural, psychological, social, spiritual, and ethical aspects
• Clinical Management
physical exercise, strength training, stress reduction, medication management, dietary recommendations, and education
• Best Practice
Given standard of care

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo HCT

Other:
• Questionnaire Administration
Ancillary studies
• Quality-of-Life Assessment
Ancillary studies
• Survey Administration
Complete surveys

Locations

Country	Name	City	State
United States	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Northwell Health Cancer Institute	New Hyde Park	New York
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California San Francisco	San Francisco	California
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Center	National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Survival after hematopoietic cell transplantation (HCT) (Phase III)		At 1 year after HCT
Primary	Change in HRQOL (Phase III)	Will be measured by the FACT-BMT.	Baseline to 90 days post-HCT
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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