Individualized Treatment Plans for Multiple Myeloma

Overseen By Andrew Cowan, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Washington

Must not be taking: Antibiotics, Immunosuppressants, Prednisone

Disqualifiers: Bleeding, Infection, Other malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to create personalized treatments for patients with multiple myeloma or plasma cell leukemia that has returned or stopped responding to other treatments. Researchers use high throughput screening, which tests many drugs simultaneously, along with genetic information to identify the best drugs for each patient. This approach could help doctors select more effective treatments tailored to each person's specific disease. Suitable candidates include patients whose multiple myeloma has returned after several treatments or who did not respond well to their first treatment. As an unphased trial, this study allows patients to contribute to groundbreaking research that could lead to more personalized and effective treatment options.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot have had previous treatments for multiple myeloma within 2 weeks of starting the study treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that previous treatments for multiple myeloma should not have been given within 2 weeks before starting the study treatment.

What prior data suggests that this high throughput screening is safe for patients with multiple myeloma or plasma cell leukemia?

Research has shown that high-throughput screening, a method for quickly testing many drugs, can help predict how patients with multiple myeloma will respond to treatments. Studies indicate that this method is generally safe and well-tolerated. For instance, one study tested 170 different compounds and found that patients did not experience severe side effects from the screening itself, suggesting its safety for people.

Although high-throughput screening is not a treatment, it aids in selecting the best possible drugs for a patient, making it a valuable tool in managing multiple myeloma, a type of cancer affecting blood cells. The goal is to find the most effective drug with the fewest side effects for each patient. Overall, research supports the safety of using high-throughput screening in this personalized approach. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about high-throughput screening for multiple myeloma because it offers a personalized approach to treatment. Unlike standard therapies that apply a one-size-fits-all strategy, this method uses advanced assays and sequencing to tailor treatment plans based on individual drug sensitivities and genetic mutations. This could potentially lead to more effective and targeted treatments, reducing trial-and-error in finding the right therapy for patients. By directly involving patients and their doctors in the decision-making process with precise data, this approach aims to improve outcomes and minimize unnecessary side effects.

What evidence suggests that high throughput screening is effective for multiple myeloma?

Research has shown that high-throughput screening can aid in treating multiple myeloma by matching drugs to a patient's specific cancer type. In this trial, patients will undergo high-throughput drug sensitivity assays and mutational analysis using next-generation sequencing. One study found that 92% of patients treated based on these tests had their disease remain stable, and 46% showed partial improvement or better. This approach uses advanced technology to quickly test many drugs, identifying which might work best for each individual. It provides doctors and patients with more information for making targeted treatment decisions. Overall, this method appears promising for improving outcomes in hard-to-treat cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Danai Dima, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory multiple myeloma or plasma cell leukemia who have tried at least three prior treatments, including an IMiD and a PI. They must be able to consent, practice birth control if applicable, have adequate organ function, and measurable disease. Excluded are those with HIV/hepatitis B/C, recent major treatments like SCT within 12 weeks, active infections requiring antibiotics within 7 days of study start.

Inclusion Criteria

Your blood test shows high levels of a specific protein called free light chain and an abnormal ratio of certain proteins in your blood.

A sample from my bone marrow or tissue with enough cells for testing has been collected.

You have a disease that can be measured by specific criteria.

Exclusion Criteria

I have another cancer that is expected to affect my life for less than a year.

Pregnant or breast feeding women

I do not have HIV or active hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

High-throughput Assay and Sequencing

Patients undergo collection of bone marrow aspirate and blood for high-throughput drug sensitivity assay and mutational analysis using next generation sequencing.

Up to 3 weeks

1 visit (in-person)

Treatment Decision

Patients and their treating physicians receive the results of the tests and make treatment decisions.

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months for 2 years

What Are the Treatments Tested in This Trial?

Interventions

• High Throughput Screening

Trial Overview

The trial tests the feasibility of using high throughput drug sensitivity screening alongside genomics data to personalize treatment for patients whose multiple myeloma or plasma cell leukemia has returned after treatment or is resistant. It involves collecting samples from patients and testing many drugs simultaneously to find effective ones based on genetic information.

How Is the Trial Designed?

Group I: Device feasibility (high-throughput assay, sequencing) Experimental Treatment 3 Interventions

Patients undergo collection of bone marrow aspirate and blood for high-throughput drug sensitivity assay and mutational analysis using next generation sequencing. Patients and their treating physicians receive the results of the tests. Treatment decisions are then made by the patients and their treating physicians.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

The study analyzed the impact of FDA-issued boxed warnings on the reporting rates of adverse drug reactions (ADRs) for multiple myeloma drugs, finding that awareness of ADRs increased significantly after warnings were issued.

Out of 10 drug/ADR combinations studied, six showed a rise in reporting rates for serious adverse events post-warning, suggesting that boxed warnings effectively enhance pharmacovigilance and awareness among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of United States Food and Drug Administration's boxed warnings on adverse drug reactions reporting rates and risk mitigation for multiple myeloma drugs. Garg, V., Raisch, DW., McKoy, JM., et al.[2021]

A clinical trial involving 25 patients with relapsed or refractory multiple myeloma successfully used high-throughput screening (HTS) of 170 compounds to predict treatment responses, with actionable results available within 5 days.

Among the 13 patients who received therapy guided by the HTS results, 92% achieved stable disease or better, highlighting the potential of personalized treatment strategies based on drug sensitivity testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Throughput Drug Screening and Multi-Omic Analysis to Guide Individualized Treatment for Multiple Myeloma. Coffey, DG., Cowan, AJ., DeGraaff, B., et al.[2023]

A 7-gene signature developed from RNA sequencing of newly diagnosed multiple myeloma patients can predict which treatment regimens (bortezomib or lenalidomide) will be more effective for individual patients, enhancing personalized therapy.

Patients treated according to this gene signature showed significantly better progression-free survival (20.1 months vs not reached) and overall survival (30.7 months vs not reached) compared to those who were not, indicating that this approach could optimize treatment outcomes in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RNA-seq of newly diagnosed patients in the PADIMAC study leads to a bortezomib/lenalidomide decision signature. Chapman, MA., Sive, J., Ambrose, J., et al.[2023]

In a study of 76 FDA-approved oncology drugs tested on 25 multiple myeloma and 15 non-Hodgkin's lymphoma cell lines, proteasome inhibitors and other agents showed the broadest effectiveness against primary multiple myeloma samples, indicating their potential as key treatments.

The research identified specific genomic biomarkers linked to drug sensitivity, such as increased responsiveness to venetoclax in patients with the t(11;14) mutation, suggesting that personalized treatment strategies could be developed based on individual genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Direct to Drug" screening as a precision medicine tool in multiple myeloma. Bonolo de Campos, C., Meurice, N., Petit, JL., et al.[2021]

The Ex vivo Mathematical Myeloma Advisor (EMMA) system can predict patient-specific responses to multiple myeloma treatments within 5 days of a bone marrow biopsy, achieving a 96% accuracy in classifying patients as responders or nonresponders.

In a study of 52 patients, EMMA identified that 60% were treated with ineffective therapies, suggesting that the platform could help optimize treatment choices and improve patient outcomes by recommending more effective drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Ex Vivo Platform for the Prediction of Clinical Response in Multiple Myeloma. Silva, A., Silva, MC., Sudalagunta, P., et al.[2021]

In a study involving 132 multiple myeloma patients and 63 physicians, it was found that patients who reported higher levels of bother from side effects experienced significantly lower health-related quality of life (HRQoL) scores, indicating a direct impact of side effects on patient well-being.

There was a notable lack of agreement between patients and physicians regarding the perception of side effects, highlighting the need for better communication in managing treatment and side effects in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world patient-reported outcomes and concordance between patient and physician reporting of side effects across lines of therapy in multiple myeloma within the USA. Ribbands, A., Boytsov, N., Bailey, A., et al.[2023]

The mass accumulation rate (MAR) assay effectively measures the drug sensitivity of multiple myeloma cells, providing a rapid and accurate way to assess how these cells respond to various standard treatments.

In clinical applications, the MAR assay successfully predicted the therapeutic responses of nine patients based on their diagnoses, suggesting it could be a valuable tool for personalizing treatment strategies in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation. Cetin, AE., Stevens, MM., Calistri, NL., et al.[2019]

This study analyzed drug and immunotherapy sensitivities in 101 bone marrow samples from 70 multiple myeloma patients, revealing that specific genetic and molecular factors, such as DNA repair pathways and EYA3 expression, influence how patients respond to treatments like proteasome inhibitors and elotuzumab.

The findings indicate that understanding the bone marrow microenvironment and individual patient characteristics can help tailor personalized treatment strategies, potentially improving clinical outcomes for multiple myeloma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma. Kropivsek, K., Kachel, P., Goetze, S., et al.[2023]

Recent advancements in multiple myeloma treatment have introduced several new drugs that significantly improve patient outcomes, each with unique mechanisms of action and side effect profiles.

The review emphasizes the importance of monitoring and managing specific adverse events associated with these new treatments, providing practical guidance for healthcare providers to enhance patient safety and care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. Ludwig, H., Delforge, M., Facon, T., et al.[2023]

A comprehensive analysis of adverse event reports for thalidomide, lenalidomide, and pomalidomide revealed significant safety signals, including thalidomide's association with cardiac disorders and lenalidomide's gastrointestinal issues, highlighting the need for careful monitoring in patients.

Pomalidomide was found to have a lower risk of venous thromboembolism compared to thalidomide and lenalidomide, making it a potentially safer option for patients, especially those with renal insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. Jiang, T., Su, H., Li, Y., et al.[2022]

The study developed an advanced preclinical platform using microfluidic technology and patient-derived tumor samples to better predict the effectiveness of cancer drugs, specifically for multiple myeloma, an incurable bone marrow cancer.

This platform successfully predicted the sensitivity of multiple myeloma cells to established treatments like bortezomib and melphalan, and it can also explore drug resistance and combinations, enhancing personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preclinical assay for chemosensitivity in multiple myeloma. Khin, ZP., Ribeiro, ML., Jacobson, T., et al.[2021]

Approximately 40% of multiple myeloma patients do not meet the criteria for phase 3 clinical trials, highlighting the need for treatment decisions that consider real-world factors like patient adherence, treatment feasibility, and quality of life.

Individual patient perspectives on treatment efficacy vary widely, necessitating a personalized approach to therapy that incorporates each patient's unique goals and experiences throughout their treatment journey.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of patients with multiple myeloma beyond the clinical-trial setting: understanding the balance between efficacy, safety and tolerability, and quality of life. Terpos, E., Mikhael, J., Hajek, R., et al.[2021]

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