Pilot Study Using Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in Hematopoietic Stem Cell Transplant Recipients

This is a randomized controlled pilot study designed to evaluate whether a drug designed to
block the physiologic effects of stress is effective at blocking stress-related gene
expression in people receiving autologous stem cell transplants (their own cells) for
multiple myeloma. Such stress-related gene expression is one way that the body is programmed
to make specific proteins under conditions of stress. These proteins are believed to
contribute to worse health outcomes. By using the drug propranolol, we aim to see whether we
might block these negative health effects of stress as occur in the cancer setting and during
the transplant process. We hypothesize that individuals taking propranolol will have more
favorable gene expression.

We will enroll 40 individuals, randomizing half to receive propranolol and half to serve as
the control group not on the study drug. Study participants will start propranolol three
weeks prior to their transplant and continue it until 30 days after the transplant. We will
explore the effect of socioeconomic status, depression, and anxiety on individuals' gene
expression response to propranolol with the idea that the more impoverished, anxious, or
depressed individuals will display an even greater change in their gene expression. Part of
the purpose of this study is also be to assess whether it is feasible to give this drug to
individuals with cancer. Results of this study may inform larger trials assessing the effects
of propranolol on cancer progression.

Inclusion Criteria:

Patients with multiple myeloma receiving an autologous HCT are eligible when the following
criteria are met:

1. 18-75 years of age

2. ≤ 1 year since initiation of systemic anti-myeloma therapy

3. Patient is scheduled for autologous hematopoietic stem cell transplant as the upfront
therapy for their multiple myeloma

4. Karnofsky Performance Status of ≥90 %; patients eligible for HCT are eligible for the
study

5. All men and women must agree to practice effective contraception during the study
period if not otherwise documented to be infertile.

Exclusion Criteria:

1. Prior autologous HCT

2. Non secretory multiple myeloma

3. Concurrent beta-blocker therapy at or within 3 weeks of study entry.

4. Previous intolerance to beta-blocker therapy

5. Any medical contraindications to beta-blocker therapy including, but not limited to,
symptomatic hypotension; drug hypersensitivity; sinus bradycardia, sick sinus
syndrome, or 2nd or 3rd degree atrioventricular block without a pacemaker;
uncompensated heart failure; or uncontrolled asthma

6. Active, untreated depression screened for by the HCT physician (Patients who screen
positive will be offered a referral to the MCW Psycho-Oncology program for further
evaluation and treatment)

7. Concurrent use of medications as specified in the protocol throughout the study or
within one week of study entry.

8. Pregnant or lactating women