Fostamatinib as a Single Agent or in Combination With Ruxolitinib for Treatment of Patients With Myelofibrosis With Severe Thrombocytopenia
Fostamatinib may improve thrombocytopenia in myelofibrosis patients with severe thrombocytopenia (platelet <50,000/microL) and allow them to initiate treatment with a JAK2 inhibitor, ruxolitinib. Additionally, fostamatinib monotherapy may also improve myelofibrosis related symptoms and splenomegaly.
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
Searching Both is inclusive of interventional and observational studies.
|Eligible Ages||18 Years and Over|
- - Confirmed diagnosis of primary myelofibrosis or post-polycythemia vera/essential thrombocythemia myelofibrosis classified as high risk, intermediate-2 risk, or intermediate 1 risk by IPSS.
- - Severe thrombocytopenia defined as platelet count < 50,000/microL (confirmed on at least two measurements over an 8-week period prior to start of study).
- - At least 18 years of age.
- - ECOG performance status ≤ 2.
- - Able to swallow pills.
- - Adequate bone marrow and organ function as defined below: - ANC ≥ 1000/microL.
- - Peripheral blood blasts ≤ 10% - Albumin > 2.7 g/dL.
- - Total bilirubin ≤ 1.5 x IULN; patients with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 x IULN.
- - AST(SGOT)/ALT(SGPT) ≤ 1.5 x IULN.
- - Creatinine clearance > 30 mL/min by Cockcroft-Gault.
- - Female subjects must be either post-menopausal for at least 1 year or surgically sterile; or, if of childbearing potential, must not be pregnant or lactating and must agree to use a highly effective method of birth control throughout the duration of the trial and for 30 days following the last dose.
- - Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
- - History of allogeneic stem cell transplant.
- - Any solid tumor or hematologic malignancy (other than myelofibrosis) requiring active treatment at the time of study entry.
- - Currently receiving any other investigational agents.
- - A history of allergic reactions attributed to compounds of similar chemical or biologic composition to fostamatinib, ruxolitinib, or other agents used in the study.
- - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, or cardiac arrhythmia.
- - Subject has uncontrolled or poorly controlled hypertension, defined as systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg, whether or not the subject is receiving anti-hypertensive treatment.
- - Pregnant and/or breastfeeding.
- - Known positive status for human immunodeficiency virus (HIV) - Chronic, active, or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier.
- - Treatment with strong CYP3A inhibitors or inducers within 14 days before the first dose of study drug.
- - Ongoing gastrointestinal medical condition such as Crohn's disease, inflammatory bowel disease, or chronic diarrhea that is not well controlled and could interfere with absorption of oral medication or be exacerbated by study medication.
- - Known hepatic cirrhosis or severe pre-existing hepatic impairment.
- - Uncontrolled coagulopathy or bleeding disorder.
- - Female patients who intend to donate eggs and male patients who intend to donate sperm during the course of this study or for 4 months after receiving the last dose of study treatment.
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|Washington University School of Medicine|
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Amy Zhou, M.D.|
|Principal Investigator Affiliation||Washington University School of Medicine|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
The disease, disorder, syndrome, illness, or injury that is being studied.
|Study Website:||View Trial Website|
Experimental: Part A: Fostamatinib
The starting dose of fostamatinib is 100 mg twice daily (BID). After the first cycle, if no major dose related safety issue is observed and the platelet count is less than 50K/microL, then the fostamatinib dose will be increased to 150 mg BID for the next 2 cycles; otherwise the dose may be continued at 100 mg BID.
Experimental: Part B: Fostamatinib + Ruxolitinib
After 3 cycles of fostamatinib monotherapy, all patients with a sustained platelet count ≥ 50K/microL, will continue on the current fostamatinib dose plus ruxolitinib at the recommended dose per standard prescribing guidelines for an additional 9 cycles. Patients who do not reach platelet count of at least 50K/microL but who achieve clinical benefit per the treating provider may continue on single agent fostamatinib for up to 12 total treatment cycles. If these patients achieve a sustained platelet count of ≥ 50K/microL at any point prior to Cycle 10 Day 1, then they may be eligible to enroll in Part B of the study and continue treatment with fostamatinib and ruxolitinib for the remainder of the study.
Drug: - Fostamatinib
Fostamatinib will be supplied by Rigel Pharmaceuticals.
Drug: - Ruxolitinib
Ruxolitinib is commercially available.
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Washington University School of Medicine
Saint Louis, Missouri, 63110
Amy Zhou, M.D.