Take part in a myelodysplastic syndromes trial

The study is testing an “investigational” compound called alvocidib. “Investigational” means that the Food and Drug Administration (FDA) has not yet approved this drug as a prescription medicine; it is only available through research studies like this. Alvocidib was previously known as flavopiridol. Alvocidib is an investigational product being developed by Tolero Pharmaceuticals for myelodysplastic syndrome.

The purpose of this research study is to determine the safety and effectiveness (how well something works) of alvocidib when used after the standard drug in patients with myelodysplastic syndrome. The study may also help us understand more about how your disease responds to the drug.

What is a clinical study?

• A clinical study is a scientific study on how a new or existing medicine, product, procedure or treatment works in people.
• Through clinical studies, doctors can find new and better ways to prevent, detect, diagnose, control and treat illnesses.
• All clinical studies are carefully monitored and regulated to ensure participant well-being.
• Participating in a clinical study is completely voluntary and will not affect the normal standard of care you receive.

What is investigational about this study?

You might be eligible to take part in this study if you have myelodysplastic syndrome (MDS), and you have not previously received any therapy (untreated), or you have received less than six (6) cycles of treatment with hypomethylating agents (HMAs) such as azacitadine. If the study progresses to Phase 2, you may be asked to take part in this study because you have de novo (cause unknown) or secondary MDS (treatment-related) and are not eligible for induction chemotherapy or stem cell transplant.

The purpose of this research study is to determine the preliminary safety and effectiveness (how well something works) of alvocidib when used after the standard drug in patients with MDS. The study will also gain information about the PK (the process by which a drug is absorbed, distributed, metabolized and eventually eliminated by the body), pharmacodynamic (PD) biomarkers (which study how the drug effects the body) and other biomarkers that may help us understand more about how your disease responds to the drug.

What happens if you decide to participate?

If you agree to take part in this study, and qualify, your participation could last approximately 4 months (including screening period, 2 treatment cycles, and follow-up), or it may last longer depending on your response to, and recovery from, treatment.  You may receive additional 28-day treatment cycles if you are tolerating it well and showing benefit from the treatment.  You will be taken off study if the disease gets worse, intolerable side effects occur, you are unable to follow study directions, your doctor thinks it is in your best interest, or the study is stopped for any reason.

What happens when you come for study visits?

During the study, the following tests and procedures will be performed, although not every test will be performed at every visit.  The tests and procedures outlined below would likely be part of your regular medical care, however they may be performed more frequently for the purposes of the study. 

If you have any questions about any of these tests and procedures, ask your study doctor and/or study staff at any time.

• You will have blood collected (about 5 tablespoons) and a bone marrow biopsy and/or aspirate performed (only if this was not performed as part of your standard of care) to assess disease status and perform cytogenetic profiling and other laboratory tests.  Some of the bone marrow sample will be used to make slides that will be sent to the Sponsor for additional evaluation, including analysis of cell abnormalities that may be present in your biopsy sample. Analysis of the samples will be limited to evaluations that are relative to the activity of the study drug.
• You will have a physical exam including height and weight
• Vital signs (blood pressure, heart rate and temperature) 
• You will have an electrocardiogram (ECG) and an echocardiogram (ECHO) or a multigated acquisition (MUGA) scan to check your heart function.
• You will have a chest radiograph if you have not had one done within the past 28 days (of receiving your first dose)

How many people will be in this study and for how long?

About 24 patients will participate in Phase 1b of this research study at approximately 10 study centers in the United States. If the study progresses to Phase 2, an additional 25 patients will be enrolled at up to 15 study centers in North America.

What are myelodysplastic syndromes?

Myelodysplastic syndromes are a group of disorders caused by poorly formed blood cells or ones that don't work properly. Myelodysplastic syndromes result from something amiss in the spongy material inside your bones where blood cells are made (bone marrow).

Treatment for myelodysplastic syndromes usually focuses on reducing or preventing complications of the disease and its treatments. In some cases, treatment might involve chemotherapy or a bone marrow transplant.

Myelodysplastic syndromes occur when something disrupts this process so that the blood cells don't mature. Instead of developing normally, the blood cells die in the bone marrow or just after entering the bloodstream. Over time, there are more immature, defective cells than healthy ones, leading to problems such as fatigue caused by anemia, infections caused by leukopenia, and bleeding caused by thrombocytopenia.

Some myelodysplastic syndromes have no known cause. Others are caused by exposure to cancer treatments, such as chemotherapy and radiation, or to toxic chemicals, such as tobacco, benzene and pesticides, or to heavy metals, such as lead.

What do I need to know about this study?

• It is essential that you go to all the study appointments and follow the directions of the study staff.
• You can withdraw from the TPI-ALV-102 Study at any time and for any reason. This will not affect the standard of care you receive.
• You can talk to the study team at any time about any questions or concerns you may have.