Lifestyle and Supportive Care for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Roswell Park Cancer Institute

Must not be taking: Beta blockers, Calcium channel blockers

Disqualifiers: Cardiac diseases, Pulmonary diseases, Diabetes, Psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1-6 months

175 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial investigates the effect of non-chemotherapeutic interventions in patients with multiple myeloma or MDS. Non-chemotherapeutic interventions such as physical activity and nutritional interventions (e.g., modifications in diet) have been shown to positively affect the immune system and improve overall quality of life. Another purpose of this study is for researchers to learn how the addition of a beta-blocker (propranolol) to the standard treatment regimen in patients with newly diagnosed multiple myeloma affects immune response and quality of life. A study from the Mayo Clinic looked at multiple myeloma patients who were on a beta-blocker while undergoing chemotherapy and found that the use of a beta-blocker resulted in improved patient survival outcomes. Non-chemotherapeutic treatment options may help decrease symptoms and improve quality of life for patients with multiple myeloma.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but if you are currently using a beta-blocker, you must stop at least 3 months before enrolling in Module C. If you are on a special diet or taking glucose-lowering medications, you may not be eligible for Module B.

What data supports the effectiveness of the drug propranolol for multiple myeloma?

Research shows that propranolol, a drug commonly used for high blood pressure, may help treat multiple myeloma by slowing cancer cell growth and increasing cell death. A study found that patients with multiple myeloma who used propranolol had better survival rates compared to those who did not use it. ^{1 2 3 4 5}

Is propranolol generally safe for humans?

Propranolol, a medication used for over 50 years to treat high blood pressure, has been shown to have some serious and non-serious side effects, including bradycardia (slow heart rate). However, it is generally considered safe when used as prescribed. ^{1 2 3 4 6}

How is the drug Propranolol unique in treating multiple myeloma?

Propranolol is unique in treating multiple myeloma because it is primarily a beta-blocker used for heart conditions, and its use in this context may focus on supportive care aspects, such as managing stress or heart-related side effects, rather than directly targeting the cancer itself. ^{7 8 9 10 11}

Research Team

Jens Hillengass, MD, PhD

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

Adults with smoldering multiple myeloma or multiple myeloma who can follow study procedures and have no major comorbidities posing a risk. Participants must consent to the study, use contraception if of child-bearing potential, and meet specific performance status criteria. Exclusions include serious health conditions like heart disease, infections, psychiatric issues that affect compliance, certain dietary restrictions for nutrition module participants, current beta-blocker users or those with contraindications to beta-blockers.

Inclusion Criteria

Show no signs of comorbidities, myeloma symptoms, or treatment side effects that would put them in danger when participating in the study according to the physician's discretion

I have just been diagnosed with multiple myeloma and have not started treatment.

I am 18 years old or older.

Exclusion Criteria

MODULE B (NUTRITION): Special diets (physician prescribed)

I have a current broken bone or severe muscle system instability that causes symptoms.

My BMI is below 18, indicating malnutrition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo various non-chemotherapeutic interventions including strength training, intermittent fasting, and beta-blocker therapy

1-6 months

Remote and in-person visits as per module requirements

Follow-up

Participants are monitored for changes in immune markers, nutritional behavior, stress-related biomarkers, and other health parameters

3-12 months

Follow-up visits every 3 months for up to 1 year

Treatment Details

Interventions

• Behavioral Intervention
• Propranolol
• Quality-of-Life Assessment
• Questionnaire Administration
• Resistance Training
• Short-Term Fasting

Trial Overview The trial is testing non-chemotherapeutic interventions such as physical activity (with necessary equipment), nutritional changes including short-term fasting (excluding diabetics on medication), and the addition of propranolol—a beta-adrenergic antagonist—to standard treatment in newly diagnosed patients before systemic therapy starts. The goal is to see how these interventions impact immune function and quality of life.

Participant Groups

Group I: Module D Experimental Treatment 2 Interventions

MDS Patients undergo strength training for 6 months.

Group II: Module C Group I (propranolol) Experimental Treatment 3 Interventions

Patients receive propranolol PO BID for 3 months.

Group III: Module B (intermittent fasting) Experimental Treatment 3 Interventions

Patients undergo intermittent fasting for 1 month. This consists of restricting all eating to a consecutive 8-hour time period each day followed by 16 consecutive hours of not eating.

Group IV: Module A (strength training, behavioral intervention) Experimental Treatment 4 Interventions

Patients undergo strength training sessions twice weekly supervised by a licensed and specialized personal trainer via the internet (e.g., remote access) for 6 months. Patients also wear a FitBit device and receive prompts via email or text on a cell phone or other electronic device to incrementally increase physical activity over 6 months.

Group V: Module C Group II (propranolol) Active Control 3 Interventions

Patients continue receiving beta-blocker regimen as per SOC for 3 months.

Propranolol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Inderal for:

• High blood pressure
• Angina pectoris
• Heart rhythm disorders
• Migraine prophylaxis
• Essential tremor
• Performance anxiety

Approved in European Union as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Approved in Canada as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Findings from Research

Propranolol demonstrates significant antiproliferative and apoptotic effects on multiple myeloma cells, with IC50 values decreasing over time (141 μM at 24 hours to 75 μM at 72 hours), indicating its potential as a treatment option.

The mechanism of action involves increased caspase-3 activity and changes in gene expression related to apoptosis, including upregulation of pro-apoptotic factors and downregulation of Bcl-2, suggesting a targeted approach to inducing cell death in cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma. Kozanoglu, I., Yandim, MK., Cincin, ZB., et al.[2021]

In a study of 1,971 newly diagnosed multiple myeloma patients, those who used beta-blockers (BB) showed significantly improved disease-specific survival (DSS) compared to patients who did not use any cardiac medications, with a hazard ratio of 0.53, indicating a 47% reduced risk of disease-specific death.

Patients using beta-blockers alone or in combination with other cardiac drugs also demonstrated better overall survival (OS) rates compared to those on non-beta-blocker cardiac medications, suggesting that beta-blockers may positively influence survival outcomes in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-blockers improve survival outcomes in patients with multiple myeloma: a retrospective evaluation. Hwa, YL., Shi, Q., Kumar, SK., et al.[2022]

A study involving six healthy adult volunteers tested four different brands of propranolol (Inderal, Ciplar, Corbeta, and Propal) to assess variations in how the body absorbs and responds to the medication.

The results showed no significant differences in the pharmacokinetic (how the drug is processed in the body) and pharmacodynamic (the drug's effects on the body) parameters among the brands, indicating they are likely interchangeable in terms of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. Biswas, NR., Garg, SK., Kumar, N., et al.[2013]

Long-acting propranolol (Inderal LA) provides a controlled release of the medication, maintaining higher plasma concentrations over 24 hours compared to conventional tablets, which helps ensure consistent beta-adrenoceptor blockade.

This formulation is equally effective for treating conditions like angina pectoris, hypertension, and hyperthyroidism, while potentially improving patient adherence to treatment due to simplified dosing regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use. Mishriki, AA., Weidler, DJ.[2019]

A study involving 44 hypertensive patients showed that a new delayed-release beta blocker formulation (INP) taken at night resulted in greater reductions in blood pressure and heart rate during the early morning hours compared to the traditional morning dose (ILA).

In beta-blocker sensitive patients, the delayed-release formulation led to a more significant decrease in cardiac workload, as indicated by a greater reduction in the double product (a measure of myocardial oxygen demand) during the critical morning period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of a chronotherapeutically administered beta blocker vs. a traditionally administered beta blocker in patients with hypertension. Neutel, JM., Rotenberg, K.[2021]

The study analyzed data from the Canadian Adverse Drug Reaction Monitoring Program to assess the potential link between propranolol hydrochloride and bradycardia, finding that the signals for bradycardia were not statistically significant despite some high calculated statistics.

Although the results did not confirm a strong association between propranolol and bradycardia, the authors suggest that further investigation using larger databases is warranted due to the observed trends.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride. Gavali, DK., Kulkarni, KS., Kumar, A., et al.[2021]

Recent studies have shown that high-cutoff hemodialysis can effectively remove free light chains in patients with renal disease related to multiple myeloma, improving their kidney function.

Updated guidelines recommend the use of levofloxacin to prevent infections and suggest effective management strategies for bone disease and anemia, which are crucial for enhancing the quality of life in myeloma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supportive Care in Multiple Myeloma. Guzdar, A., Costello, C.[2020]

Older adults with multiple myeloma face unique challenges in treatment due to their increased susceptibility to chemotherapy-related toxicities and pre-existing health conditions, making careful management essential.

Despite these challenges, intensive therapies like autologous hematopoietic cell transplant (AHCT) should still be considered for older patients, as advancements in treatment options and multi-drug regimens can improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacologic management of multiple myeloma in older adults. Dempsey, JL., Johns, A., Rosko, AE., et al.[2023]

Recent therapies for multiple myeloma have significantly improved overall survival rates for both newly diagnosed and relapsed patients, highlighting the effectiveness of these treatments.

The International Myeloma Foundation Nurse Leadership Board has identified key patient needs, such as bone health and mobility, and created a survivorship care plan to help manage these issues effectively throughout the patient's care journey.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survivorship care guidelines for patients living with multiple myeloma: consensus statements of the International Myeloma Foundation Nurse Leadership Board. Bilotti, E., Faiman, BM., Richards, TA., et al.[2021]

The chapter provides an overview of supportive measures that can help prevent complications associated with multiple myeloma, enhancing patient safety during treatment.

These measures aim to improve patient wellbeing while undergoing specific anti-myeloma therapies, highlighting the importance of comprehensive care in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supportive therapy in multiple myeloma. Ludwig, H., Zojer, N.[2018]

The role of pharmacists in managing multiple myeloma has become crucial as advancements in treatment have turned it into a chronic disease, with pharmacists providing essential counseling on new therapies and supportive care for patients.

The pharmacist-led 'Virtual Multiple Myeloma Clinic' has been effective in optimizing patient care by offering personalized monitoring and support for patients on oral immunomodulatory therapies, highlighting the importance of pharmacists in the healthcare team.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multidisciplinary Professional Roles Addressing Needs in Multiple Myeloma: An Innovative 'Virtual' Pharmacist Surveillance Clinic. Ebied, M., Chan, V.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Beta-blockers improve survival outcomes in patients with multiple myeloma: a retrospective evaluation. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Comparison of a chronotherapeutically administered beta blocker vs. a traditionally administered beta blocker in patients with hypertension. [2021]

6. India pubmed.ncbi.nlm.nih.gov

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Supportive Care in Multiple Myeloma. [2020]

8. England pubmed.ncbi.nlm.nih.gov

The pharmacologic management of multiple myeloma in older adults. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Survivorship care guidelines for patients living with multiple myeloma: consensus statements of the International Myeloma Foundation Nurse Leadership Board. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Supportive therapy in multiple myeloma. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Multidisciplinary Professional Roles Addressing Needs in Multiple Myeloma: An Innovative 'Virtual' Pharmacist Surveillance Clinic. [2021]