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

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.

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)