Fostamatinib for Post-Transplant Cytopenias
Recruiting in Palo Alto (17 mi)
Overseen byRichard W Childs, M.D.
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Must not be taking: Fostamatinib, Cytokine-targeting biologics
Disqualifiers: Severe psychiatric illness, Uncontrolled hypertension, others
No Placebo Group
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?Background:
People who have a blood stem cell transplant can sometimes develop cytopenia. This means that their levels of one or more types of blood cell, such as the red cells or platelets, are lower than they should be. This can occur because a person s immune system might attack these cells after a stem cell transplant. Cytopenia can lead to anemia, severe bleeding, infections, and other problems. Treatments are needed to help keep blood cell levels stable after blood stem cell transplant.
Objective:
To test a study drug (fostamatinib) in people who have cytopenia after a blood stem cell transplant.
Eligibility:
People aged 18 to 75 years who have cytopenia after a blood stem cell transplant.
Design:
Participants will be screened. They will have a physical exam. They will have blood, urine, and stool tests.
Fostamatinib is an oral tablet taken by mouth. Participants will take the pills 2 times a day for 12 weeks.
Participants will have a medical assessment every 2 weeks; their vital signs will be checked, and they will have blood and stool tests. Participants must come to the NIH clinic for these visits in weeks 4 and 12. Other visits may be done by telephone or telehealth; the blood and stool tests can be sent to the researchers from a local lab.
After 4 weeks, some participants may begin taking a higher dose of the drug.
Participants will return for a final medical assessment 2 weeks after they finish taking the drug.
Participants who complete this study and show evidence that fostamatinib has increased their blood cell counts may enroll in an extension study to continue taking fostamatinib.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it requires that any standard treatments for GVHD or cytopenias be stable for at least 15 days before joining. It's best to discuss your specific medications with the trial team.
Is fostamatinib generally safe for humans?
Fostamatinib has been studied for conditions like immune thrombocytopenia and is generally considered safe, with most side effects being mild or moderate, such as headaches and diarrhea, which can be managed by adjusting the dose.
12345How is the drug Fostamatinib unique for treating post-transplant cytopenias?
Fostamatinib is unique because it is an oral drug that works by inhibiting spleen tyrosine kinase (SYK), a pathway involved in platelet destruction, which is different from other treatments that may not target this specific mechanism. It has shown durable responses in conditions like chronic immune thrombocytopenia, suggesting potential benefits for post-transplant cytopenias where standard treatments may not exist.
13467Eligibility Criteria
Adults aged 18-75 with low blood cell counts after a stem cell transplant can join. They must use effective birth control, not have HIV/HBV/HCV, and be stable on current medications. Excluded are those with uncontrolled hypertension, recent biologic treatments, severe psychiatric issues, certain liver abnormalities, or other autoimmune causes of low blood cells.Inclusion Criteria
I have been on a stable dose of my current medication for GVHD or cytopenias for at least 15 days.
I am between 18 and 75 years old.
Peripheral blood or bone marrow T-cell chimerism >=50% donor cells
+8 more
Exclusion Criteria
I have a low white blood cell count.
I have ITP or wAIHA linked to lymphoma, chronic leukemia, hepatitis, or HIV.
My high blood pressure is not under control.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive oral fostamatinib twice daily for 12 weeks
12 weeks
6 visits (in-person), additional visits (virtual)
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 weeks
1 visit (in-person)
Open-label extension (optional)
Participants who show improvement may continue taking fostamatinib
Participant Groups
The trial is testing fostamatinib tablets taken twice daily for 12 weeks to treat cytopenia in post-stem cell transplant patients. Participants will undergo regular medical assessments including physical exams and various tests at NIH clinics or via telehealth.
1Treatment groups
Experimental Treatment
Group I: Fostamatinib ArmExperimental Treatment1 Intervention
The subjects will receive oral fostamatinib daily for 12 weeks.
Fostamatinib is already approved in United States for the following indications:
🇺🇸 Approved in United States as Tavalisse for:
- Chronic immune thrombocytopenia (ITP)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Heart, Lung, and Blood Institute (NHLBI)Lead Sponsor
References
Fostamatinib for the treatment of immune thrombocytopenia in adults. [2021]The pharmacology, pharmacokinetics, efficacy, safety, dosing and administration, and place in therapy of fostamatinib, a novel spleen tyrosine kinase inhibitor for the treatment of adult immune thrombocytopenia that has had an insufficient response to a previous treatment are summarized.
Fostamatinib for the treatment of Japanese patients with primary immune thrombocytopenia: A phase 3, placebo-controlled, double-blind, parallel-group study. [2023]Fostamatinib, a spleen tyrosine kinase inhibitor, has been approved for the treatment of chronic primary immune thrombocytopenia (ITP) in the United States, Canada and some European countries. We conducted a phase 3, placebo-controlled, double-blind, parallel-group study to evaluate the efficacy and safety of fostamatinib in Japanese patients with primary ITP. Thirty-four patients were randomised to fostamatinib (n = 22) or placebo (n = 12) at 100-150 mg twice a day for 24 weeks. Stable responses (platelet ≥50 000/μl at ≥4 of the 6 visits from weeks 14 to 24) were observed in eight (36%) patients on fostamatinib and in none of the patients on placebo (p = 0.030). Overall responses (platelet ≥50 000/μl at ≥1 of the 6 visits from weeks 2 to 12) were seen in 10 (45%) patients on fostamatinib and in none of the patients on placebo (p = 0.006). Patients on fostamatinib required rescue medication less often and experienced fewer bleeding symptoms than patients on placebo. Adverse events observed were mild or moderate and were manageable. No new safety signals were identified in Japanese patients with ITP.
Pharmaceutical Approval Update. [2020]Fostamatinib (Tavalisse) for thrombocytopenia in adults with chronic immune thrombocytopenia; coagulation factor Xa (recombinant), inactivated-zhzo (Andexxa) for the reversal of anticoagulation; epoetin alfa-epbx (Retacrit), a biosimilar for the treatment of anemia.
Sustained response off therapy after fostamatinib: A chronic refractory ITP case report. [2023]Fostamatinib is a SYK-inhibitor drug recently approved by the FDA and EMA for treating chronic immune thrombocytopenia. This drug induces a response in about 40% of patients and has a good toxicity profile. It is known that discontinuing thrombopoietin receptor agonists (TRAs) with the maintenance of sustained response off therapy is possible. On fostamatinib, we do not yet have such information. In this case report, we describe the story of a woman with a multirefractory immune thrombocytopenia (steroids, splenectomy, rituximab, both available TRAs). After 16 years from diagnosis, she started fostamatinib therapy within a clinical trial and achieved a complete response. Grade 1-2 headache and diarrhea occurred during the first months of therapy. These adverse events were resolved with dose reduction of fostamatinib. Despite the dose reduction, the platelet count remained steadily above 80 × 109/L. After 4 years, fostamatinib was gradually reduced and finally discontinued with no drop in platelet count. This is the first case in which fostamatinib discontinuation resulted in a sustained response off therapy.
Effects of Fostamatinib on the Pharmacokinetics of Oral Contraceptive, Warfarin, and the Statins Rosuvastatin and Simvastatin: Results From Phase I Clinical Studies. [2021]Fostamatinib is a spleen tyrosine kinase inhibitor that has been investigated as therapy for rheumatoid arthritis and immune thrombocytopenic purpura. The present studies assessed the potential for pharmacokinetic interaction between fostamatinib and the commonly prescribed medications oral contraceptive (OC), warfarin, and statins (rosuvastatin, simvastatin) in healthy subjects.
Fostamatinib for the treatment of chronic immune thrombocytopenia. [2021]Fostamatinib is a spleen tyrosine kinase inhibitor recently approved for the treatment of chronic immune thrombocytopenia (ITP) in patients without adequate response to at least 1 prior line of therapy. This article reviews fostmatinib's mechanism of action and its clinical safety and efficacy in 2 industry-sponsored multicenter phase 3 randomized controlled trials in North America, Australia, and Europe (FIT1 and FIT2). Cost comparisons are discussed as well as the role of fostamatinib in relation to other options for chronic ITP.
Fostamatinib in chronic immune thrombocytopenia: a profile of its use in the USA. [2022]Oral fostamatinib is an orally administered small molecule spleen tyrosine kinase (SYK) inhibitor approved for the treatment of adults with chronic immune thrombocytopenia (ITP) who have an inadequate response to a previous treatment. Fostamatinib has a unique mechanism of action, whereby its active metabolite targets the SYK-mediated pathway of platelet destruction. In clinical trials, fostamatinib provided durable responses in adults with chronic ITP who had not responded or had relapsed following treatment with one or more prior ITP therapies, including corticosteroids, thrombopoietin receptor agonists, rituximab, and/or splenectomy. Most patients who respond to fostamatinib maintain platelet counts of > 50 × 109/L for periods of ≥ 12 months. The most common adverse events reported with fostamatinib in clinical trials were diarrhea, hypertension, nausea, and increased transaminase levels.