This scar tissue is caused by abnormal blood stem cells in the bone marrow, which divide too quickly, leading to decreased marrow function and inflammation both within the bone marrow and throughout the body. As a result of progressive bone marrow failure, subjects often become increasingly anaemic and dependent on frequent blood transfusions over time. In addition, the spleen attempts to compensate for poor blood cell production causing it to become enlarged (known as splenomegaly). The enlarged spleen itself may cause discomfort, pain, fatigue and a decreased appetite adding to the symptoms caused by chronic inflammation, low blood cell production, and disease burden.
Classified as a myeloproliferative neoplasm (MPN), myelofibrosis can arise on its own or as a progression from polycythaemia vera (post-PV-MF) or essential thrombocythaemia (post-ET-MF).
From the outside, many people with myelofibrosis look the same as their healthy friends and family. But inside, subjects are often experiencing:
Impaired Blood Cell Production:
Reduced red blood cells (anaemia), white blood cells (leukopenia), and platelets (thrombocytopenia)
Fatigue/tiredness, night sweats, itching, bone pain, inactivity, concentration problems, and weight loss
Enlarged Spleen (Splenomegaly):
Abdominal pain, a feeling of early fullness, bloating and high pressure in the liver vasculature
The MOMENTUM Clinical Trial for Subjects with Myelofibrosis will evaluate the effectiveness and safety of the investigational drug, momelotinib, compared to another drug (danazol), in treating myelofibrosis. Subjects who participate in the clinical trial will randomly be assigned so that 120 subjects receive momelotinib and 60 subjects receive danazol, for a total of 180 subjects.
Momelotinib is a type of drug known as a Janus kinase (or JAK) inhibitor which is designed to address the three major problems of myelofibrosis including the debilitating symptoms; anaemia (low red blood cell counts), or other low blood cell counts; and an enlarged spleen. Because momelotinib inhibits the JAK enzymes and another enzyme target involved in red blood cell production, called ACVR1, it may be able to treat myelofibrosis symptoms and enlarged spleen while also increasing red blood cell numbers, improving anaemia. This profile makes momelotinib different to other JAK inhibitors currently available which do not treat anaemia and usually make it worse.
Momelotinib treatment will be compared to that of Danazol. Danazol has not been approved by Health Canada to treat myelofibrosis, but is recommended by clinical practice guidelines as a treatment for anemia in subjects with myelofibrosis. It works in a completely different way to momelotinib and is not a JAK inhibitor.
Momelotinib is a potential new drug for myelofibrosis which has already been investigated in more than 820 myelofibrosis subjects in earlier studies. Subjects who wish to participate in the new MOMENTUM Clinical Trial will first be required to pass a period of screening to ensure they are suitable to enter the trial.
The screening period may last for up to 6 weeks prior to the first treatment dose. You will be asked to come in for a visit to speak with your doctor and nursing staff and ensure you meet all of the requirements for the MOMENTUM Clinical Trial.
The trial drug treatment period consists of two phases. In the first phase you will receive either momelotinib or danazol along with an inactive placebo as a part of your trial drug dosing. These drugs can be taken orally at home every day for 24 weeks.
In the second phase, which starts after you have been taking the trial drug for 24 weeks, you will be offered to stay on your treatment from the first phase or switch to momelotinib, depending on what treatment you were originally assigned to. Treatment in the second phase can continue for up to 4 years if you and your doctor believe momelotinib is safe for you and you are receiving benefit from treatment.
During the first year, you will visit the site every 4 weeks and then every 3 months after that.
You will be asked to return to the trial site 30 days after your last treatment dose, and then you will be contacted by trial staff periodically after that.
You or someone you know may be eligible for the MOMENTUM Clinical Trial if you/they:
Are 18 years of age or older
Have received a diagnosis of myelofibrosis
Are currently or were previously treated with an approved JAK inhibitor (including either ruxolitinib or fedratinib) for myelofibrosis for a period of greater than 3 months (or greater than 28 days if blood related side-effects were experienced while on the drug)
Are anaemic AND have a significant symptom burden according to the definition used in the clinical trial protocol
A number of other criteria must be met before you/they may participate in the clinical trial. Your doctor and nursing staff will be familiar with what these requirements are and will be able to discuss these with you.
An investigational drug is tested in the laboratory and clinical trials by scientists and doctors for research purposes, but it is not yet approved for commercial sale. A clinical trial tests the safety and efficacy of an investigational drug, in addition to how well it works to address therapeutic needs of the disease.
Research trials are carefully designed to assess investigational drugs. Specific criteria are developed to determine if you are eligible to participate, you must follow a consistent drug dosing regimen and attend scheduled clinic visits, and you will undergo medical/behavioural tests and assessments. A team of trial coordinators, nurses and doctors works closely with you throughout the process to monitor any symptoms or changes, and to collect information on how you are feeling and reacting to the treatment. The information collected during the course of the trial is carefully reviewed, verified and analysed to determine the risks and benefits of the investigational drug. Generally, favourable results from more than one trial are needed before an investigational drug can be approved for sale to the public.
Your rights, well-being, and safety are of the utmost importance to the clinical trial staff during and beyond the trial. Staff will explain all aspects of the trial to you and will answer any questions you may have. All clinical trials must follow strict guidelines on how participants are treated. The trial has been reviewed and approved by an Ethics Committee and/or Institutional Review Board, which are independent bodies set up to safeguard people taking part in medical research.
It is important to remain in the clinical trial for its entire duration, but you have the right to leave at any time and for any reason. If you do decide to leave the trial, ensure you speak with the trial doctor first to determine how it may affect your health and what other treatment options are available.
You will not be paid to participate in this trial. You may receive reimbursement for reasonable travel expenses to attend your trial visit. A member of the clinical trial team will explain this in detail to you.
Additional information regarding this investigational drug and clinical trial can be found on clinicaltrials.gov, on this website or on sierraoncology.com.