Understanding Clinical Trials in Myeloma
The International Myeloma Foundation (IMF) is the global leader in multiple myeloma, reaching more than 525,000 patients in 140 countries. The IMF mission is to improve the quality of life of myeloma patients while working toward prevention and a cure. The IMF vision is to realize a world where every myeloma patient can live life to the fullest, unburdened by the disease. Since 1990, the IMF has been serving the myeloma community through the following four pillars:
RESEARCH At the IMF, finding a cure for myeloma is our top priority. The IMF Scientific Advisory Board (SAB) of leading myeloma experts identifies key opportunities to drive research forward. The IMF Black Swan Research Initiative® is pushing the boundaries with early screening for a precursor condition of myeloma as well as cure-focused myeloma clinical trials. The IMF International Myeloma Working Group (IMWG) provides trusted guidelines for diagnosing, treating, and managing myeloma. The IMF also funds innovative research through its Brian D. Novis Research Grants.
EDUCATION Myeloma is a complex and unique journey for each patient. The IMF offers hundreds of free publications in multiple languages to help navigate the myeloma journey. IMF seminars, webinars, and workshops directly connect patients with expert clinicians. The IMF Nurse Leadership Board (NLB) provides recommendations for managing myeloma. The IMF M-Power Project works to break down barriers and ensure health equity in underserved populations.
SUPPORT The IMF offers more than 160 myeloma support groups across North America, including specialized groups for Spanish-speakers, people with smoldering disease, care partners of patients with myeloma, and patients without care partners. The IMF InfoLine helps with your myeloma-related questions. The IMF “Myelo” AI chatbot helps you find the right resources. You don’t have to face myeloma alone. Studies show that social support can greatly improve the quality of life of people with cancer.
ADVOCACY In the U.S., the IMF Advocacy team represents your interests at the federal and state levels. Internationally, the IMF Global Myeloma Action Network (GMAN) works to improve patient access to treatments.
Visit myeloma.org or contact the IMF InfoLine at 1.818.487.7455 (worldwide) or 1.800.452.CURE (U.S. and Canada), or infoline@myeloma.org.
You are not alone
The International Myeloma Foundation (IMF) is here to help you. The IMF is committed to providing information and support for patients with multiple myeloma (which we refer to simply as “myeloma”) and their care partners, friends, and family members.
We achieve this through a broad range of resources available on our website myeloma.org, and through numerous programs and services such as seminars, webinars, workshops, and the IMF InfoLine, which consistently provides the most up-to-date and accurate information about myeloma in a caring and compassionate manner. Contact the IMF InfoLine at 1.818.487.7455 or InfoLine@myeloma.org.
What you will learn from this booklet
Myeloma is a cancer that is not known to most patients at the time of diagnosis. If you have myeloma, it is important and helpful for you to learn about your disease, its treatment options, and supportive care measures in order to play an active role in your own medical care and to make good decisions about your care in partnership with your doctor.
If you are a patient with myeloma, we suggest that you read the IMF’s publication, Patient Handbook for Multiple Myeloma, which will help you to better understand this disease. In addition, this booklet will direct you to resources that may be relevant in your particular case. All IMF publications are free-of-charge and can be read, downloaded, or requested in printed format at publications.myeloma.org.
The IMF’s Understanding-series publications address specific drugs, drug classes, and combination therapies used to treat myeloma. These booklets also discuss supportive care measures that may help manage the symptoms and side effects of myeloma and its treatments. The IMF’s publication, Understanding Your Test Results, explains how myeloma is diagnosed, monitored, and assessed throughout the disease course.
Words in bold+blue type are explained in the IMF’s companion publication, Understanding Myeloma Vocabulary, a comprehensive glossary that also can be helpful in discussions with your doctor. Myeloma is complicated, but the language that describes it doesn’t have to be hard to understand.
If you are reading this booklet in electronic format, the light blue links will take you to the corresponding resources.
This booklet discusses clinical trials in myeloma. A clinical trial is a medical research study with people who volunteer to test scientific approaches to a new treatment or a new combination therapy.
A clinical trial may give you access to treatment that is not yet available outside of a study setting. Whether or not you might benefit from participation in a clinical trial is one of the critical discussions that a patient should have with their treating doctor.
Goals of clinical trials
Clinical research in myeloma has become a robust field, with the National Cancer Institute (NCI) website cancer.gov listing more than 1,000 clinical trials for myeloma. The IMF has partnered with SparkCures to help myeloma patients and their care partners identify and explore myeloma clinical trials across the U.S., as well as to access personalized clinical trial support resources that may be helpful to them. Visit myeloma.org/sparkcures for more information.
Every clinical trial is designed to find better ways to prevent, detect, diagnose, or treat cancer and to answer scientific questions. A clinical trial is launched only after laboratory studies have demonstrated the potential of a new drug, treatment, or procedure to work better than existing methods, and also have outlined the potential safety. The goal of conducting myeloma clinical trials is to improve patient care by determining if a new drug or treatment is more effective and/or has fewer or less harmful side effects than existing treatments.
Diversity in clinical trials
Historically, there has been a lack of diverse representation in clinical trials in general and in myeloma clinical trials in particular. In the U.S., approximately 20% of all myeloma patients are of African descent, but only 5%–8% of patients in myeloma clinical trials are of African descent. This is significant for the following reasons:
¡ All patients of all races and ethnicities should be able to benefit from clinical trials.
¡ Diverse patient representation in clinical trials is required to ensure that the outcomes are applicable to all patients.
Reasons for underrepresentation in clinical trials are complex and include systemic racism, accessibility of clinical trials, sensitivity to diversity by medical professionals, misconduct in medicine in the past, the lack of trust in the system, and more.
Increasing diverse representation
Multisystem challenges of improving healthcare equity require multisystem solutions. The myeloma community must unite to work together to overcome this disparity. This is part of the objective of the IMF’s M-Power nationwide initiative to improve the short-term and long-term outcomes of patients with myeloma in Black communities.
To ensure that clinical trials reflect the diversity of the myeloma patient population, M-Power is bringing together regulators, pharmaceutical companies, healthcare systems and providers, as well as patient advocates and their care partners.
Best practices are being developed for designing clinical trials, appointing diversity officers, setting appropriate patient accrual, engaging the community at large, and including non-traditional clinical trial sites to improve access to all. Visit mpower.myeloma.org for more information.
The partnership of doctors, patients, and care partners
The critical “frontlines” of clinical trials are found in the discussions between doctors and patients and their care partners. The following tips can help myeloma patients communicate with their doctors as they consider participating in a clinical trial:
¡ Talk openly and honestly with your doctor. Discuss the purpose of the proposed clinical trial, as well as its potential benefits and the possible risks.
¡ Include in your discussion the family members or other trusted individuals who can help you with decision-making.
¡ Be aware how the history of mistrust of the medical establishment may influence your thinking about clinical trials.
¡ Do not rush the discussion. Ask all your questions and raise all your concerns, and make sure that they are addressed.
¡ Engage with local and national advocacy groups, such as the IMF, and take part in support groups that encourage dialogue and foster your understanding of clinical trials.
¡ Be sure that you understand the discussions. Ask that explanations are repeated or presented to you in ways that you are comfortable with. If your native language is not English, you can ask that a translator is provided to you.
¡ Secure as much support as possible for the logistics of participating in a clinical trial, including travel assistance, home care, meals, accommodations, etc.
¡ Have a clear understanding about the financial implications of the clinical trial, if any.
When to participate in a clinical trial
Clinical trials have the opportunity to offer new therapies for myeloma that are not approved by the U.S. Food and Drug Administration (FDA).
In clinical trials, researchers don’t know if the new method will be better than standard of care (SOC) therapy for patients who are being treated now. What researchers do know is that some clinical trials will result in better treatments for patients in the future.
Taking part in a clinical trial is voluntary. Not all clinical trials are right for every patient. Potential participation in a clinical trial should be discussed in depth with your physician and healthcare team. Before agreeing to participate, patients must learn about possible risks of the therapy being studied and what other options for treatment are available.
Eligibility criteria
There are certain conditions and requirements that patients must meet in order to be enrolled in a clinical trial. When all study subjects meet the same eligibility criteria, it provides researchers with consistent data needed to answer the main question of the study.
Eligibility requirements are based on the type of clinical trial. Examples of eligibility may include age, performance status, type and stage of cancer, certain medical tests, laboratory results, other illnesses, and past treatments received.
The eligibility criteria for each clinical trial have two sections: inclusion criteria and exclusion criteria. Inclusion criteria determine who may participate in the clinical trial. Exclusion criteria are conditions that determine if a patient may not be able to participate in a study. Both the inclusion and exclusion criteria are a vital part of the research plan to get credible and consistent results.
Informed consent
Informed consent is the process that requires a doctor to give a patient enough information about a procedure, strategy, or clinical trial – including the issues of risks, benefits, alternatives, and potential costs – for the patient to make an informed decision about whether or not to consent to the proposed treatment.
Medical progress and patient safety
Clinical trials are used to further test new medications and therapies on human subjects. Clinical trials are performed using protocols that adhere to accepted standards of patient safety, informed consent, and data interpretation. Strict regulation of clinical trials helps to ensure that the balance between medical progress and patient safety is carefully maintained.
Vocabulary of clinical trials
¡ Accrual – The process of enrolling patients in a clinical trial, or the number of patients already enrolled or anticipated to be enrolled in a clinical trial.
¡ Arm – A treatment group in a randomized study, in which there are two or more arms.
¡ Cohort – A group of patients in the same study receiving the same treatment or placebo.
¡ Control group – The arm of a randomized clinical trial that receives the standard of care treatment or placebo.
¡ Dose-limiting toxicity (DLT) – When the side effects of the treatment are severe enough to prevent giving more of the same treatment.
¡ Double-blind – When neither the patient nor the investigator knows the arm of the trial to which the patient is randomized. The purpose is to eliminate any bias in the reporting of results.
¡ Endpoint – The goal of the study. A clinical trial endpoint may aim to measure toxicity, response rate, or survival.
¡ Experimental group – The arm of a randomized trial that gets the new treatment.
¡ Maximum-tolerated dose (MTD) – The highest dose of a treatment that most people can safely withstand.
¡ Placebo – An inert (inactive) substance often used in clinical trials for comparison with an experimental drug. No clinical trial for cancer patients in the U.S. can ethically or legally randomize patients to receive a placebo alone when they require treatment. In the placebo arm of a cancer treatment trial, patients receive treatment with approved therapy plus a placebo.
¡ Progression-free survival (PFS) – The length of time during and after the treatment of myeloma that a patient lives with the disease but the myeloma does not get worse. In a clinical trial, PFS is one way to measure how well the treatment is working.
¡ Progressive disease – Myeloma that is becoming worse or relapsing, as documented by tests. Defined as an increase of ≥ 25% from the lowest confirmed response value in the myeloma protein level and/or new evidence of disease.
¡ Randomized clinical trial – A study in which patients are randomly assigned to receive a particular treatment.
¡ Refractory – Disease that is no longer responsive to standard of care treatments. Myeloma is refractory in patients who have had progressive
disease either during treatment or within 60 days following treatment. Most clinical trials for advanced disease are for patients with relapsed and/or refractory myeloma.
Phases of a clinical trial
Phase I clinical trial
The main goal of a phase I clinical trial is to determine the maximumtolerated dose (MTD) and safety profile of a new drug or a new combination of drugs. A phase I study may be the first testing of a new treatment in humans. Please note that in combination therapies, the individual elements may have been already well-tested in humans.
Generally, patients enrolled in phase I clinical trials have advanced myeloma that is refractory to standard of care treatment. A cohort may have 3–6 patients who are given the same treatment at the same dose. The first cohort typically gets a low dose, which is then increased in each subsequent cohort until a set number of patients experience dose-limiting toxicity (DLT). The dose level used for the previous cohort is then taken to be the MTD, which is then used as the dose in a phase II trial.
Phase II clinical trial
A study designed to determine the efficacy and safety of a new therapy that has been tested in a phase I trial. Patients are usually required to have measurable disease that is refractory to any standard of care (SOC) treatment. If the results of a phase II study are clearly much better than the SOC treatment, then the treatment may be approved without being tested in a phase III study. If results from a phase II study are promising, the treatment may then be tested in a phase III study.
Phase III clinical trial
A study that compares two or more treatments. The endpoint of a phase III study may be survival or PFS. Phase III studies are usually randomized, so patients don’t choose which treatment they receive. Some phase III trials compare a new treatment that had good results in a phase II study with a standard of care treatment; other phase III studies compare treatments that are already in common use.
Phase IV clinical trial
Even after a drug has been approved by the FDA for use in a particular indication, there may be need for additional studies. For example, safety surveillance is designed to detect any rare or long-term side effects over a larger patient population and longer time period than was possible during the phase I–III clinical trials.
