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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

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ClinicalTrials.gov Identifier: NCT03870750
Recruitment Status : Not yet recruiting
First Posted : March 12, 2019
Last Update Posted : July 17, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Tracking Information
First Submitted Date  ICMJE March 8, 2019
First Posted Date  ICMJE March 12, 2019
Last Update Posted Date July 17, 2019
Estimated Study Start Date  ICMJE August 15, 2019
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 8, 2019)
  • Improvement in HRQOL (Phase II) [ Time Frame: First 90 days after HCT ]
    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.
  • Survival after hematopoietic cell transplantation (HCT) (Phase III) [ Time Frame: At 1 year after HCT ]
  • Change in health-related quality of life (HRQOL) (Phase III) [ Time Frame: Baseline to 90 days post-HCT ]
    Will be measured by the FACT-BMT.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03870750 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2019)
  • Rate of overall survival [ Time Frame: Up to 1 year ]
    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.
  • Non-relapse mortality [ Time Frame: At 90 days and up to 1 year ]
    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.
  • Cumulative incidence of relapse [ Time Frame: Up to 1 year ]
    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.
  • Relapse-free survival [ Time Frame: Up to 1 year ]
    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.
  • Cumulative incidence of frailty [ Time Frame: Up to 1 year ]
    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.
  • Cumulative incidence of disability [ Time Frame: Up to 1 year ]
    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.
  • Frequency of hospitalization [ Time Frame: Up to 90 days after HCT ]
    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.
  • Duration of each hospitalization [ Time Frame: Up to 90 days after HCT ]
    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.
  • Number of admissions to intensive care unit [ Time Frame: Up to 90 days after HCT ]
    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.
  • Duration of admissions to intensive care unit [ Time Frame: Up to 90 days after HCT ]
    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.
  • Days out of hospital alive [ Time Frame: Up to 90 days after HCT ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief 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.
Detailed Description

PRIMARY OBJECTIVES:

I. Compare in a randomized phase II study the effectiveness of supportive and palliative care, a clinical multi-modal program, or a combined approach versus usual care only (UCO) to determine the winning arm in improving health-related quality of life (HRQOL) (Day-90 Functional Assessment of Cancer Therapy-Bone Marrow Transplant [FACT-BMT] scores) for vulnerable recipients of allogeneic hematopoietic cell transplantation (HCT). (Phase II) II. Compare in a randomized phase III study the effectiveness of the winning arm from the preceding phase II study versus UCO in improving HRQOL (Day-90 FACT-BMT scores) and/or overall survival at 1-year for vulnerable recipients of allogeneic HCT. (Phase III)

SECONDARY OBJECTIVES:

I. Rates of overall survival. (Phase II and III) II. Cumulative incidences of non-relapse mortality (NRM). (Phase II and III) III. Cumulative incidences of relapse. (Phase II and III) IV. Rates of relapse-free survival (RFS). (Phase II and III) V. Cumulative incidence of frailty. (Phase II and III) VI. Cumulative incidence of disability. (Phase II and III) VII. Cumulative incidence of grades III-IV cardiac, hepatic, pulmonary and renal toxicities according to the Common Toxicity Criteria (CTC) version 4. (Phase II) VIII. Use of resources within first 90 days after HCT: Frequency of hospitalization. (Phase II and III) IX. Use of resources within first 90 days after HCT: Duration of each hospitalization. (Phase II and III) X. Use of resources within first 90 days after HCT: Number and duration of admissions to intensive care unit. (Phase II and III) XI. Use of resources within first 90 days after HCT: Days out of hospital alive (DOHA). (Phase II and III)

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Allogeneic Hematopoietic Stem Cell Transplantation Recipient
  • Hematopoietic and Lymphoid Cell Neoplasm
  • Non-Neoplastic Hematologic and Lymphocytic Disorder
Intervention  ICMJE
  • 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:
    • Comfort Care
    • palliation
    • palliative care
    • palliative therapy
    • Palliative Treatment
    • Symptom Management
    • Symptoms Management
  • Other: Clinical Management
    physical exercise, strength training, stress reduction, medication management, dietary recommendations, and education
  • Other: Best Practice
    Given standard of care
    Other Names:
    • standard of care
    • standard therapy
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo HCT
    Other Names:
    • Allogeneic Hematopoietic Cell Transplantation
    • Allogeneic Stem Cell Transplantation
    • HSC
    • HSCT
  • Other: Questionnaire Administration
    Ancillary studies
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Survey Administration
    Ancillary studies
Study Arms  ICMJE
  • 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.
    Interventions:
    • Other: Supportive Palliative Care
    • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    • Other: Questionnaire Administration
    • Other: Quality-of-Life Assessment
    • Other: Survey Administration
  • 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..
    Interventions:
    • Other: Clinical Management
    • Other: Best Practice
    • Other: Questionnaire Administration
    • Other: Quality-of-Life Assessment
    • Other: Survey Administration
  • 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..
    Interventions:
    • Other: Supportive Palliative Care
    • Other: Clinical Management
    • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    • Other: Questionnaire Administration
    • Other: Quality-of-Life Assessment
    • Other: Survey Administration
  • 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.
    Interventions:
    • Other: Best Practice
    • Other: Questionnaire Administration
    • Other: Quality-of-Life Assessment
    • Other: Survey Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 8, 2019)
600
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2024
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Vulnerable patients as defined by one or more of the following criteria

    • Aged 65 years or older
    • Having Hematopoietic Cell Transplantation - Comorbidity Index (HCT-CI) scores of >= 3
    • Having frailty as determined by walk speed of < 0.8 m/s using 4-meter walk test
  • 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
  • Stated willingness to comply with study procedures and reporting requirements
  • 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
  • Adequate cardiopulmonary reserve, as judged by self-reported ability to 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mohamed Sorror 206-667-6298 msorror@fredhutch.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03870750
Other Study ID Numbers  ICMJE RG1004746
NCI-2019-01097 ( Registry Identifier: NCI / CTRP )
9885 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Fred Hutchinson Cancer Research Center
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Mohamed Sorror Fred Hutch/University of Washington Cancer Consortium
PRS Account Fred Hutchinson Cancer Research Center
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP