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

Not Applicable

Recruiting

• Conditions: Plasma Cell Myeloma; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Smoldering Plasma Cell Myeloma
• Interventions: Behavioral: Behavioral Intervention; Drug: Propranolol; Drug: Beta-Adrenergic Antagonist; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Other: Short-Term Fasting; Other: Resistance Training

• Registration Number: NCT05312255
• Lead Sponsor: Roswell Park Cancer Institute

Brief Summary

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.

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 and other hematologic 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 and other hematologic 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 and other hematologic disorders.

OUTLINE: Patients are assigned to Module A, B C or D. (MDS patients will only be assigned in Module D)

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.

MODULE D: Patients will receive resistance training twice a week for 6 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 Timeline

• Study First Submitted: 2022-03-18
• Study First Submitted QC: 2022-03-28
• Study First Posted: 2022-04-05
• Study Start: 2022-06-28
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-21
• Last Update Posted: 2024-11-25
• Primary Completion: 2027-06-28
• Study Completion: 2027-06-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 175

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
  • Module D: ECOG 0-1

• MODULE A, B and C: Have a diagnosis of smoldering multiple myeloma, multiple myeloma or plasma cell leukemia (PCL) or

• MODULE D: non transfusion dependent low-risk MDS

• 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 and D (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 MODULE D: Patients with MDS not necessitating transfusion therapy at time of enrollment (no transfusion within 8 weeks prior to enrollment) i.e. patients on observation, or receiving growth factors or luspatercept only

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
• MODULE D: Cardiovascular disease which is deemed limiting exercise readiness by a cardiologist

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Module A (strength training, behavioral intervention)	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.
Module A (strength training, behavioral intervention)	Quality-of-Life Assessment	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 A (strength training, behavioral intervention)	Questionnaire Administration	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 A (strength training, behavioral intervention)	Resistance Training	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 (intermittent fasting)	Quality-of-Life Assessment	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 B (intermittent fasting)	Questionnaire Administration	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 B (intermittent fasting)	Short-Term 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.
Module C Group I (propranolol)	Propranolol	Patients receive propranolol PO BID for 3 months.
Module C Group I (propranolol)	Quality-of-Life Assessment	Patients receive propranolol PO BID for 3 months.
Module C Group II (propranolol)	Quality-of-Life Assessment	Patients continue receiving beta-blocker regimen as per SOC for 3 months.
Module C Group II (propranolol)	Questionnaire Administration	Patients continue receiving beta-blocker regimen as per SOC for 3 months.
Module D	Behavioral Intervention	MDS Patients undergo strength training for 6 months.
Module D	Resistance Training	MDS Patients undergo strength training for 6 months.
Module C Group I (propranolol)	Questionnaire Administration	Patients receive propranolol PO BID for 3 months.
Module C Group II (propranolol)	Beta-Adrenergic Antagonist	Patients continue receiving beta-blocker regimen as per SOC for 3 months.

Primary Outcome Measures

Name	Time	Method
Changes in immune cell subsets	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).

Secondary Outcome Measures

Name	Time	Method
Changes in the gut microbiome	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	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	3 months	Dexa (bone density scan) will be performed at 1 and 3 months
Changes in stress	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	At 1 and 3 months	As assessed by the Generalized Anxiety Disorder 7-item Scale
Changes in fatigue as assessed by EORTC-LQLQ-FA12	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	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	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	Up to 6 months	Will be evaluated using a linear mixed model and will be used to compare mean levels between timepoints.

Trial Locations

Locations (1)

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States