At some point in the care continuum, cancer clinical trials can be a treatment option for many patients. Clinical research in multiple myeloma has become a robust field with the National Cancer Institute (NCI) website cancer.gov listing more than 1,000 clinical trials.

A clinical trial is a research study of new treatment that involves patients as participants. Each study is designed to find better ways to prevent, detect, diagnose, or treat cancer and to answer scientific questions. Clinical trials may offer patients access to promising treatments that have not yet been approved, but have been studied in a laboratory setting and may have already been studied in other multiple myeloma patients. The experimental drugs used in clinical trials are free of charge to the patient. Some trials do not involve new drugs, but instead test new combinations of drugs that have already been tested and approved.

What Are the Phases of a Clinical Trial?

Phase I

A phase I trial is designed to determine the maximum-tolerated dose (MTD) of a new drug or a new combination of drugs that has never been tried in humans. It is usually the first human testing of a new treatment, although in phase I trials of combination therapies, the individual elements may already have been well tested. Generally, patients in phase I trials will have advanced cancer that is refractory to any standard treatment.

In a typical phase I trial, successive groups (“cohorts”) of 3 to 6 patients are given the treatment. All patients in a cohort get the same dose. The first cohort typically gets a very low dose, and the dose is 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. This MTD is then used in a phase II trial.

Phase II

A phase II trial is designed to determine the response rate of a new single agent or combination therapy that has already been tested in phase I trials. Typically, 14 to 50 patients with one type of cancer are treated to see how many have a response. Patients are usually required to have advanced cancer that is refractory to any standard treatment. In addition, they must have measurable disease.

If results from a phase II trial are promising enough, the treatment may then be tested in a phase III trial. If the results are obviously much better than the standard treatment, then it may not be necessary to do a phase III trial, and the treatment may become standard based on phase II trial results.

Phase III

The end point of a phase III trial is usually survival or progression-free survival (PFS, or remission duration). Phase III trials are usually randomized, so patients don’t choose which treatment they receive. A typical phase III trial has fifty to thousands of patients.

Phase III trials are usually designed so that patients are separated into groups called “arms” to compare one or more therapies to a standard treatment. The patients who receive the experimental therapy are in the “experimental arm,” and the patients who receive the standard treatment are in the “control" or "comparator" arm. Often, neither the patients nor the researchers conducting the trial know to which arm any patient has been randomized, and thus the term “double-blind” is used. Randomized trials are designed to produce data that is truly unbiased by expectations. Sometimes the patients in one arm of a study do much better than the patients in the other arm, and then the study is “unblinded” and the patients are all given the better therapy.

Some phase III trials compare a new treatment that has had good results in phase II trials with an older, well-known, standard treatment. Other phase III trials compare treatments that are already in common use. Some treatments in phase III trials may be available outside the clinical trial setting.

The best measure of the success of a therapy is overall survival (OS), but it can take years or even decades to follow patients on a clinical trial to see how long they survive. In order to find a shorter measure of a drug’s efficacy, most trials for multiple myeloma therapies currently use PFS. A concerted effort is currently being mounted by a consortium including the IMF to have the U.S. Food and Drug Administration (FDA) approve minimal residual disease (MRD) as a new endpoint for clinical trials.

Phase IV

Even after a drug has been approved by the FDA for use in a particular indication, additional safety surveillance and ongoing technical support may be needed. Post-FDA-approval studies (also known as phase IV trials) may be required by regulatory authorities or may be undertaken by the sponsoring company for a variety of reasons, such as finding a new market, testing for interactions with other drugs, or treating certain population groups that are not otherwise well represented in clinical trials. The 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.

What's Next?