This research study is a pilot study, meaning it is the first-time investigators are examining the oral inhibitors Trametinib and Dabrafenib as a potential treatment for  multiple myeloma patients. The U.S. Food and Drug Administration (FDA) has not yet approved these drugs for multiple myeloma, but they have been approved for other uses.

Some cancers have changes (mutations) in the BRAF, KRAS or NRAS genes. These three genes produce proteins that are all involved in sending signals in cells that can lead to cell growth. Certain mutations in these three genes cause a change in these proteins that can increase the growth and spread of cancer cells.
   
Dabrafenib and trametinib work to prevent these altered proteins from sending signals in cancer cells, and thereby may block the growth and spread of cancer cells in cancers with BRAF, KRAS, or NRAS gene mutations. Dabrafenib and trametinib have been used in the treatment of different cancers in other research studies, and information from those research studies suggest that these agents may help to kill multiple myeloma cells.

Participants who are interested in this study will have their tumor tissue undergo genetic testing to detect for BRAF, KRAS, and NRAS gene mutations. As part of this test, the DNA sequence of genes other than BRAF, KRAS, or NRAS may be determined at the same time.

Not everyone who participates in this research study will receive the same drugs. The type and dose of the drug will depend on the type of mutation that was detected in your multiple myeloma tissue. The below summarizes what type of treatment will be received depending on the genetic mutation detected.

• KRAS gene: trametinib taken orally once per day.
• NRAS gene: trametinib taken orally once per day.
• BRAF gene (V600): dabrafenib taken orally twice per day OR dabrafenib taken orally twice per day and trametinib taken orally once per day
• BRAF gene (non-V600): dabrafenib taken orally twice per day and trametinib taken orally once per day

Each study treatment cycle lasts 4 weeks. Safety and tolerability will be assessed once a month through collecting labs and a physical examination. Some other procedures that participants will have to complete throughout the study include a  bone marrow biopsy and x-rays. Some of these procedures are part of your routine care for multiple myeloma.

Participants can continue to receive study treatment for as long as their disease does not get worse, experience serious side effects, and the study doctor feels it is in their best interest to continue to receive dabrafenib and/or trametinib.