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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Non-Neoplastic Hematologic and Lymphocytic Disorder
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Other: Survey Administration; Other: Best Practice; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Other: Supportive Palliative Care; Other: Clinical Management

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 620
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Mohamed Sorror, MD, MSc; Phone Number: 206-667-6298; Email: msorror@fredhutch.org

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Cancer Institute Palo Alto
      • Contact: Laura Johnston, MD; Phone Number: 650-723-0822
      • Principal Investigator: Laura Johnston, MD
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco
      • Principal Investigator: Rebecca Olin, MD
      • Contact: Rebecca Olin, MD; Phone Number: 415-353-2063; Email: rolin@medicine.ucsf.edu
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Wayne State University/Karmanos Cancer Institute
      • Contact: Joseph Uberti, MD, PhD; Phone Number: 313-576-8760; Email: ubertij@karmanos.org
      • Principal Investigator: Joseph Uberti, MD, PhD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota/Masonic Cancer Center
      • Contact: Mukta Arora, MD; Phone Number: 612-626-4105
      • Principal Investigator: Mukta Arora, MD
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Hassan Alkhateeb; Email: Alkhateeb.Hassan@mayo.edu
      • Principal Investigator: Hassan Alkhateeb, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
      • Principal Investigator: Ronald Sobecks, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
      • Contact: Rachel Cook, MD, MS; Phone Number: 503-494-8945
      • Principal Investigator: Rachel Cook, MD, MS
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • Contact: Tiffany Sherrill; Phone Number: 832-824-7995; Email: thsherri@texaschildrens.org
      • Principal Investigator: George Carrum, MD
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutch/University of Washington Cancer Consortium
      • Contact: Mohamed Sorror, MD, MSc; Phone Number: 206-667-6298; Email: msorror@fredhutch.org
      • Principal Investigator: Mohamed Sorror, MD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (SPC); 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: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Survey Administration; Complete surveys; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo HCT; Other Names: Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation; Other: Supportive Palliative Care; focuses on relieving symptoms of stress from serious illness and care through physical, cultural, psychological, social, spiritual, and ethical aspects; Other Names: Symptom Management; Comfort Care; Palliative Treatment; PA-Palliative Therapy; palliation; Symptoms Management; palliative care; palliative therapy
Experimental: Arm II (CMC); 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: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Survey Administration; Complete surveys; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo HCT; Other Names: Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation; Other: Clinical Management; physical exercise, strength training, stress reduction, medication management, dietary recommendations, and education
Experimental: Arm III (SPC and CMC); 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: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Survey Administration; Complete surveys; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo HCT; Other Names: Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation; Other: Supportive Palliative Care; focuses on relieving symptoms of stress from serious illness and care through physical, cultural, psychological, social, spiritual, and ethical aspects; Other Names: Symptom Management; Comfort Care; Palliative Treatment; PA-Palliative Therapy; palliation; Symptoms Management; palliative care; palliative therapy; Other: Clinical Management; physical exercise, strength training, stress reduction, medication management, dietary recommendations, and education
Active Comparator: Arm IV (standard of care); 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: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Survey Administration; Complete surveys; Other: Best Practice; Given standard of care; Other Names: standard of care; standard therapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Mohamed Sorror, MD, MSc, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2019
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: March 8, 2019
• First Posted (Actual): March 12, 2019

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases
• Other Study ID Numbers: RG1004746; NCI-2019-01097 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 9885 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); R01CA227092 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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