Non-chemotherapeutic Interventions for the Improvement of Quality of Life and Immune Function in Patients With Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT05312255
• Recruitment Status: Recruiting
• First Posted: April 5, 2022
• Last Update Posted: October 25, 2023
• Sponsor: Roswell Park Cancer Institute
• Information provided by (Responsible Party): Roswell Park Cancer Institute

Tracking Information

• First Submitted Date: March 18, 2022
• First Posted Date: April 5, 2022
• Last Update Posted Date: October 25, 2023
• Actual Study Start Date: June 28, 2022
• Estimated Primary Completion Date: June 28, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 27, 2023)

Changes in immune cell subsets [ Time Frame: At baseline and at 1 year ]

Will be assessed by flow cytometry, comparing levels before and after one of three lifestyle interventions (physical exercise, intermittent fasting, beta blocker therapy). Will use a linear mixed model. Since the form of the model is unknown a priori, the power calculations are based on comparing any two timepoints using a two-sided paired t-test. With n=100, we have 80% power (at alpha = 0.05/3) to detect a difference of at least 0.33 standard deviations (SD).

Original Primary Outcome Measures (submitted: March 28, 2022)

• Changes in immune cell subsets [ Time Frame: At baseline and at 1 year ]
  Will be assessed by flow cytometry, comparing levels before and after one of three lifestyle interventions (physical exercise, intermittent fasting, beta blocker therapy). Will use a linear mixed model. Since the form of the model is unknown a priori, the power calculations are based on comparing any two timepoints using a two-sided paired t-test. With n=100, we have 80% power (at alpha = 0.05/3) to detect a difference of at least 0.33 standard deviations (SD).
• Adherence rate (Selinexor Substudy) [ Time Frame: At baseline, 3 and 6 months ]
  proportion of patients without clinical or serological progression remaining on study at 3 and 6 monthswho achieved ≥ 80% of physical exercise targets.

Current Secondary Outcome Measures (submitted: March 28, 2022)

• Changes in the gut microbiome [ Time Frame: At 1 and 3 months ]
  Fecal samples will be collected and compared from group with physical exercise,compared to group doing intermittent fasting).
• Comparison in bone markers [ Time Frame: At 1 and 3 months ]
  Will be assessed from intermittent fasting serum samples compared to serum samples of those doing physical exercise.
• Changes in body composition [ Time Frame: 3 months ]
  Dexa (bone density scan) will be performed at 1 and 3 months
• Changes in stress [ Time Frame: At 1 and 3 months ]
  Significant differences among groups in the mean Perceived Stress Scale (PSS) score, which measures the stress severity perceived by the subjects in the last month. The scale is constituted by 10 items that are self-rated by the subject on a 0-4 Likert scale. The scale minimum total score is 0, the maximum is 40. Higher total scores indicate a worse outcome
• Changes in anxiety [ Time Frame: At 1 and 3 months ]
  As assessed by the Generalized Anxiety Disorder 7-item Scale
• Changes in fatigue as assessed by EORTC-LQLQ-FA12 [ Time Frame: At 1 and 3 months ]
  12-item multidimensional fatigue questionnaire.The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). The range is 3. For the raw score, less points are considered to have a better outcome.
• Change in functional status [ Time Frame: At 1 and 3 months ]
  basic assessment of physical activity before diagnosis will be compared to one administered at follow up
• Changes in nutritional behavior before and after intermittent fasting [ Time Frame: Up to 5 months ]
  Will be modeled using a GEE logistic model. Rates of positive nutritional behavior will be compared beween time points.
• Changes in stress-related biomarkers [ Time Frame: Up to 6 months ]
  Will be evaluated using a linear mixed model and will be used to compare mean levels between timepoints.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Non-chemotherapeutic Interventions for the Improvement of Quality of Life and Immune Function in Patients With Multiple Myeloma
• Official Title: Improving Host Factors in Patients With Monoclonal Gammopathies
• Brief Summary: This clinical trial investigates the effect of non-chemotherapeutic interventions in patients with multiple myeloma. 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.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the impact of different lifestyle and low side effect interventions (exercise, nutrition, stress effects reduction) on immune markers in patients with monoclonal plasma cell disorders.

SECONDARY OBJECTIVES:

I. To assess the impact of different lifestyle and low side effect interventions (exercise, nutrition) on bone turnover parameters, body composition, the microbiome and physical fitness in patients with monoclonal plasma cell disorders.

II. To assess the impact of different lifestyle and low side effect interventions (exercise, nutrition, stress effect reduction) on parameters of stress, mental health and quality of life in patients with monoclonal plasma cell disorders.

OUTLINE: Patients are assigned to Module A, B or C.

MODULE A: 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.

MODULE B: 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.

MODULE C: Patients are assigned to group 1 (are not currently taking beta-blockers) or group 2 (current taking beta-blockers).

GROUP I: Patients receive propranolol orally (PO) twice daily (BID) for 3 months.

GROUP II: Patients continue receiving beta-blocker regimen as per standard of care (SOC) for 3 months.

After completion of the study interventions, patients in module A are followed every 3 months for 1 year. Patients in module B are followed at 3 and 5 months. Patients in module C are followed for 3 months.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Plasma Cell Myeloma
• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma
• Smoldering Plasma Cell Myeloma

Intervention

• Behavioral: Behavioral Intervention
  Wear a FitBit device and receive prompts for 6 months
  Other Names:

  • Behavior Conditioning Therapy
  • Behavior Modification
  • Behavior or Life Style Modifications
  • Behavior Therapy
  • Behavioral Interventions
  • Behavioral Modification
  • Behavioral Therapy
  • Behavioral Treatment
  • Behavioral Treatments
• Drug: Beta-Adrenergic Antagonist
  Receive beta-blocker regimen as per SOC
  Other Names:

  • Beta Blocker
  • Beta-Adrenergic Blocking Agent
  • Beta-Blockers
• Drug: Propranolol
  Given PO
  Other Name: 1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol
• Other: Quality-of-Life Assessment
  Ancillary studies
  Other Name: Quality of Life Assessment
• Other: Questionnaire Administration
  Ancillary studies
• Other: Resistance Training
  Undergo strength training for 6 months
  Other Name: Strength Training
• Other: Short-Term Fasting
  Participate in intermittent fasting
  Other Names:

  • Intermittent Fasting
  • Short-term Intermittent Fasting

Study Arms

• Experimental: Module A (strength training, behavioral intervention)
  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.
  Interventions:

  • Behavioral: Behavioral Intervention
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
  • Other: Resistance Training
• Experimental: Module B (intermittent fasting)
  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.
  Interventions:

  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
  • Other: Short-Term Fasting
• Experimental: Module C Group I (propranolol)
  Patients receive propranolol PO BID for 3 months.
  Interventions:

  • Drug: Propranolol
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
• Active Comparator: Module C Group II (propranolol)
  Patients continue receiving beta-blocker regimen as per SOC for 3 months.
  Interventions:

  • Drug: Beta-Adrenergic Antagonist
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 5, 2022): 150
• Original Estimated Enrollment (submitted: March 28, 2022): 220
• Estimated Study Completion Date: June 28, 2026
• Estimated Primary Completion Date: June 28, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age >= 18 years of age

• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of:

  • Module A: ECOG 0 - 1
  • Module B: ECOG 0 - 2
  • Module C: ECOG 0 - 2
• Have a diagnosis of smoldering multiple myeloma or multiple myeloma
• 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
• Are able to understand and follow assessment and intervention procedures
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
• MODULE A (PHYSICAL ACTIVITY): Participant has access to a personal computer or tablet with camera, microphone, speakers and internet access
• MODULE B (NUTRITION): Not applicable
• MODULE C (BETA BLOCKER): Newly diagnosed patients with multiple myeloma necessitating treatment and before initiation of systemic therapy
• MODULE C: Female participants of child-bearing potential must have a negative pregnancy test at study entry and then agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Male patients with female partners of child-bearing potential should also use adequate contraceptive methods (see above). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

Exclusion Criteria:

• Major comorbidities that would cause danger to the patient when participating in the study and that would have a risk of progression if the patient took part in the study (including, but not limited to): cardiac or pulmonary and infectious diseases (e.g., ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia) or, psychiatric illness/social situations that would limit compliance with study requirements
• Unwilling or unable to follow protocol requirements
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to take part in study intervention (comorbidities, myeloma symptoms, treatment side effects)
• MODULE A (PHYSICAL ACTIVITY): Current and symptomatic pathological fracture(s) or severely advanced instability of the musculo-skeletal system that is deemed to making the patient unsafe to participate. This will be assessed by radiologist, a neurosurgeon and/or an orthopedic surgeon, if applicable.
• MODULE A (PHYSICAL ACTIVITY): Current and symptomatic pathological fracture(s) or severely advanced instability of the musculo-skeletal system
• MODULE A (PHYSICAL ACTIVITY): Acute bone instability as assessed by whole body low-dose computed tomography and evaluated by an experienced surgeon
• MODULE B (NUTRITION): Clinical signs of malnutrition (body mass index [BMI] < 18)
• MODULE B (NUTRITION): Special diets (physician prescribed)
• MODULE B (NUTRITION): Diabetic treated with glucose-lowering medications and/or insulin
• MODULE B (NUTRITION): Other reasons not to withhold food
• MODULE B (NUTRITION): Any condition which in the investigator's opinion deems the participant an unsuitable candidate to limit food consumption
• MODULE C (BETA BLOCKER): Current use of a beta blocker (includes all non-selective and beta-1 selective blockers) or, use of a beta-blocker within 3 months of study enrollment
• MODULE C (BETA BLOCKER): Contraindications to the use of beta-blockers, e.g.; severe sinus bradycardia; sick sinus syndrome; or heart block greater than first-degree, uncontrolled depression, unstable angina pectoris, uncontrolled heart failure (New York Heart Association [NYHA] Grade III or IV), hypotension ( systolic blood pressure < 100 mmHg), severe asthma or chronic obstructive pulmonary disease (COPD), uncontrolled type I or type II diabetes mellitus (HbA1C > 8.5 or 12h fasting plasma glucose > 160 mg/dL at screening), symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma, current calcium channel blocker use (Non-dihydropyridines such as verapamil) or rhythm control agents such as digoxin and amiodarone. Patients with pacemakers will be excluded
• MODULE C (BETA BLOCKER): Pregnant or nursing female participants, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05312255
• Other Study ID Numbers: I 1680221; NCI-2022-01918 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); I 1680221 ( Other Identifier: Roswell Park Cancer Institute )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Roswell Park Cancer Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Roswell Park Cancer Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jens Hillengass; Roswell Park Cancer Institute

• PRS Account: Roswell Park Cancer Institute
• Verification Date: October 2023