Clinical Trials: Demystifying Their Role in Multiple Myeloma Patient Care and Outcomes

Clinical Trials

Joseph Mikhael MD, MEd, FRCPC

Chief Medical Officer, International Myeloma Foundation

Professor, Translational Genomics Research Institute, City of Hope Cancer Center

Yelak Biru

President and CEO , International Myeloma Foundation

28-year Myeloma Patient

Objectives

• Provide The Rationale For Clinical Trials

• Outline The Phases Of Clinical Trials

• Discuss The Risks And Benefits Of Clinical Trials

• Listen To Patients Who Have Been On A Clinical Trial

Clinical TrialsOverview

Remember some of the important principles of clinical trials:

• The drive of research has brought us to where we are

• No one is expected to be a “guinea pig” with no potential benefit to them

• Research is under very tight supervision and standards

• Open, clear communication between the physician and the patient is fundamental

Clinical Trials

Myths

MYTH: If I participate in a clinical trial, I might get a placebo, not active treatment

MYTH: If I participate in a clinical trial, I can’t change my mind

• Phase 1 and 2, everyone gets active treatment

• Phase 3 standard of care vs new regimen: often standard regimen with/without additional agent in MM trials

• Patients can withdraw their consent for clinical trial participation at any time

MYTH: Clinical trials are dangerous because they have new medicines and practices

• Some risk is involved with every treatment, but medicines are used in clinical trials with people only after they have gone through testing to indicate that the drug is likely to be safe and effective for human use

MYTH: Clinical trials are expensive and not covered by insurance

• Research costs are typically covered by the sponsoring company

• Standard patient care costs are typically covered by insurance

• Check with clinical trial team/insurers; costs such as transportation, hotel, etc may not be reimbursed and are paid by patient

Clinical Trials –Why Me??

• Every patient is unique and must be viewed that way

• Benefits of trials are numerous and include:

• Early access to “new” therapy

• Delay use of standard therapy

• Contribution to myeloma world –present and future

• Financial access to certain agents

• Must be balanced with potential risks

• “Toxicity” of side effects

• Possibility of lack of efficacy

Overview of New Drug Development

Identify a target for therapy in the laboratory

Confirm the anticancer activity in laboratory and animal studies

Clinical trials (human studies) to determine safety, dosing and effectiveness

The whole process costs millions of dollars and years of effort!

Even Before Phase I

• Most agents are tested in lab models

• Various “myeloma cell lines”, also known as “in vitro”

• Next step is animal model

• We are more like mice than you think!!

• Earliest study in Phase I is called “First in Human”

• Often uses extremely low dose of drug to ensure safety

Phase 1 Clinical Trials

• All patients receive the experimental therapy

• Phase 1 trials find the optimal dose of a new drug or drug combination

• Patients get higher doses as the study continues

• Determine side effects of new drugs or combinations

• Explore how the drug is metabolized by the body

• Important for all stages of myeloma

• Determine if a new drug or combination is effective against the cancer

Phase 2 Clinical Trials

• May be added to a Phase 1 study once the ideal dose is found

• Patients usually receive the experimental therapy

• In some cases, the study may include two “arms” comparing either two different doses or a different treatment (another combination of drugs)

Phase 3 Clinical Trials

• Highest form of clinical evidence. Typically, a large number of patients are required…usually required for full FDA approval

• Patients receive either an experimental therapy (one or more drugs) or the current standard treatment

o The patient is randomly assigned to a treatment—a process called “randomization”

o Neither the physician or the patient can determine which treatment is given

• May be placebo controlled, if no standard treatments are available

• Very closely monitored for effectiveness and side effects

Preclinical

ANIMAL STUDIES: Examine safety and potential for efficacy

FIRST INTRODUCTION OF AN INVESTIGATIONAL DRUG INTO HUMANS

• Determine metabolism and PK/PD actions, MTD, and DLT

• Identify AEs

• Gain early evidence of efficacy, studied in many conditions; typically, 20 to 80 patients; everyone gets agent

Clinical Trials Phases

EVALUATION OF EFFECTIVENESS IN A CERTAIN TUMOR TYPE

• Determine short-term AEs and risks; closely monitored

• Includes up to 100 patients, typically

GATHER ADDITIONAL EFFECTIVENESS AND SAFETY INFORMATION

COMPARED TO STANDARD OF CARE

• Placebo may be involved if no standard of care exists; hundreds to several thousand patients

• Often multiple institutions; single or double blind; sometimes open label

APPROVED AGENTS IN NEW POPULATIONS OR NEW DOSE FORMS

Benefits of Participati on

Possible benefits:

• Patients will receive, at a minimum, the best standard treatment

• If the new treatment or intervention is proven to work, patients may be among the first to benefit

• Patients have a chance to help others and improve cancer care

Risks of Participati on Possible risks:

• New treatments or interventions under study are not always better than, or even as good as, standard care

• Even if a new treatment has benefits, it may not work for every patient

• Health insurance and managed care providers do not always cover clinical trials

Why Do So Few Cancer Patients Participate in Trials?

Patients may:

• Be unaware of clinical trials

• Lack access to trials

• Fear, distrust, or be suspicious of research

• Have practical or personal obstacles

• Face insurance or cost problems

• Be unwilling to go against their physicians’ wishes

• Not have physicians who offer them trials

• Have a disconnect with their healthcare team

Diversity in Clinical Trials

There has been a lack of diverse representation in clinical trials in myeloma.

• 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.

Importance of Participation by Diverse Populations in Clinical Trials

[P]eople from racial and ethnic minorities and other diverse groups are underrepresented in clinical research. This is a concern because people of different ages, races, and ethnicities may react differently to certain medical products.

– FDA

Leadership and commitment

Community engagement practices

Investigator hiring, training, and mentoring practices

Patient engagement practices

FDA = US Food and Drug Administration.

Regnante JM, et al. J Oncol Pract. 2019;15(4):e289-e299. FDA website. Clinical Trial Diversity. Accessed March 27, 2024. https://www.fda.gov/consumers/minority-health-and-health-equity/clinical-trial-diversity.

US Cancer Centers of Excellence: Strategies for Increased Inclusion of Racial and Ethnic Minorities in Clinical Trials