Fostamatinib for Post-Transplant Cytopenias

Overseen By Jamie Y Hur, D.O.

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests fostamatinib, an oral medication, to determine its effectiveness for individuals with low blood cell counts (cytopenia) following a blood stem cell transplant. Cytopenia can cause anemia, infections, and bleeding. The trial seeks participants with cytopenia due to immune system issues that have not improved with other treatments and who require regular blood transfusions or rely on steroids. Participants will take the medication for 12 weeks, with regular health check-ins. If fostamatinib increases blood cell counts, participants may have the option to continue treatment in an extension study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that fostamatinib is likely to be safe for humans?

Research shows that fostamatinib is generally well-tolerated. Previous studies found most side effects to be mild or moderate, with diarrhea, high blood pressure, nausea, and increased liver enzymes being the most common. For most participants, these side effects were not severe.

The FDA has already approved fostamatinib for treating chronic immune thrombocytopenia, a condition that can cause easy or excessive bruising and bleeding. This approval indicates the drug's safety for humans with that condition, but individual reactions can vary. Trial participants will receive close monitoring and can discuss any side effects with the trial doctors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fostamatinib is unique because it targets the condition of post-transplant cytopenias through a different mechanism than current treatments. While most existing options focus on stimulating blood cell production, fostamatinib works by inhibiting the spleen tyrosine kinase (SYK) pathway, which plays a role in the immune system's regulation of blood cells. This novel approach has the potential to address the root cause of the cytopenias, rather than just managing symptoms. Researchers are excited about fostamatinib because its oral administration offers a more convenient alternative to other treatments, which often require injections or infusions.

What evidence suggests that fostamatinib might be an effective treatment for post-transplant cytopenias?

Research has shown that fostamatinib may help increase blood cell counts. In earlier studies, 56% of patients who took fostamatinib experienced improved platelet counts within four weeks. Another study found that 68% of patients maintained a stable response over 12 months, with an average platelet count of 111. These results suggest that fostamatinib could improve blood cell levels in people with low blood cell counts after a stem cell transplant. In this trial, participants will take oral fostamatinib daily for 12 weeks to confirm these effects specifically for low blood cell counts after a transplant, and the existing data appears promising. ^{2 3 4 6 7}

Who Is on the Research Team?

Jamie Y Hur, D.O.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

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.

Peripheral blood or bone marrow T-cell chimerism >=50% donor cells

I understand this study is experimental and I can give my consent.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Fostamatinib

Trial Overview 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.

How Is the Trial Designed?

Group I: Fostamatinib Arm Experimental Treatment 1 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)

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Fostamatinib is an oral spleen tyrosine kinase inhibitor that effectively increases platelet counts in adults with immune thrombocytopenia who did not respond adequately to previous treatments, as shown in two Phase III trials.

The treatment is generally well tolerated, with lower rates of severe bleeding-related side effects, although common adverse events include diarrhea, nausea, and liver function test elevations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostamatinib for the treatment of immune thrombocytopenia in adults. Moore, DC., Gebru, T., Muslimani, A.[2021]

Fostamatinib (Tavalisse) is effective for treating thrombocytopenia in adults with chronic immune thrombocytopenia, helping to increase platelet counts.

Coagulation factor Xa (recombinant), inactivated-zhzo (Andexxa) is used for reversing anticoagulation effects, providing a critical intervention for patients experiencing bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

Fostamatinib, a recently approved SYK-inhibitor for chronic immune thrombocytopenia, showed a complete response in a patient who had previously failed multiple treatments, indicating its efficacy in difficult cases.

This case is notable as it demonstrates that fostamatinib can be safely discontinued after achieving a sustained response, with the patient's platelet count remaining stable even after reducing and stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained response off therapy after fostamatinib: A chronic refractory ITP case report. Auteri, G., Biondo, M., Mazzoni, C., et al.[2023]

Fostamatinib significantly increases the exposure to ethinyl estradiol in oral contraceptives, with a 28% increase in AUC and a 34% increase in Cmax, while it does not affect levonorgestrel levels.

Fostamatinib causes substantial drug-drug interactions with statins, increasing rosuvastatin AUC by 96% and simvastatin AUC by 74%, but it does not have a clinically relevant effect on warfarin pharmacokinetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Fostamatinib on the Pharmacokinetics of Oral Contraceptive, Warfarin, and the Statins Rosuvastatin and Simvastatin: Results From Phase I Clinical Studies. Martin, P., Gillen, M., Ritter, J., et al.[2021]

Fostamatinib is an effective treatment for chronic immune thrombocytopenia (ITP) in patients who have not responded adequately to at least one prior therapy, as demonstrated in two phase 3 randomized controlled trials (FIT1 and FIT2) across North America, Australia, and Europe.

The drug works by inhibiting spleen tyrosine kinase, which plays a crucial role in the immune response, thereby helping to increase platelet counts in ITP patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostamatinib for the treatment of chronic immune thrombocytopenia. Connell, NT., Berliner, N.[2021]

Fostamatinib is an effective oral treatment for adults with chronic immune thrombocytopenia (ITP) who have not responded to previous therapies, showing durable responses and maintaining platelet counts above 50 × 10^9/L for at least 12 months.

The drug works by inhibiting the spleen tyrosine kinase (SYK) pathway, which is involved in platelet destruction, but it can cause side effects such as diarrhea, hypertension, nausea, and increased liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostamatinib in chronic immune thrombocytopenia: a profile of its use in the USA. McKeage, K., Lyseng-Williamson, KA.[2022]

In a phase 3 study involving 34 Japanese patients with chronic primary immune thrombocytopenia (ITP), fostamatinib demonstrated significant efficacy, with 36% of patients achieving stable platelet responses compared to none in the placebo group.

Fostamatinib also led to fewer bleeding symptoms and a reduced need for rescue medication, with adverse events being mild to moderate and manageable, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostamatinib for the treatment of Japanese patients with primary immune thrombocytopenia: A phase 3, placebo-controlled, double-blind, parallel-group study. Kuwana, M., Ito, T., Kowata, S., et al.[2023]

Citations

1. tavalissehcp.com tavalissehcp.com/efficacy

TAVALISSE® (fostamatinib disodium hexahydrate) tablets ROBUST IMPROVEMENTS IN PLATELET COUNTS WERE OBSERVED AFTER PRIOR STEROID AND/OR TPO-RA USE · 56% of 2nd-line patients responded within 4 weeks · 76% of 2nd-line ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05502783

Using Fostamatinib to Treat Post-Hematopoietic Stem Cell ... This open label phase II trial is designed to evaluate the efficacy of fostamatinib in the treatment of post-transplant cytopenias as assessed by hematologic ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK599019/

Fostamatinib (Tavalisse) - NCBI Bookshelf - NIH In the FIT2 trial, 18% of patients in the fostamatinib group experienced stable platelet response compared to 4% in the placebo group (RD = 14%; 95% CI, 0.5 to ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6223701/

Fostamatinib in chronic immune thrombocytopenia Among 117 patients who received fostamatinib for ≥ 12 months, 17 of 25 (68%) maintained a stable response, with a median platelet count of 111 ...

5. rigel.com rigel.com/investors/news-events/press-releases/detail/290/rigel-announces-post-hoc-data-analysis-of-tavalisse-in

Rigel Announces Post-hoc Data Analysis of TAVALISSE® ... In this analysis, 32 patients received fostamatinib as a second-line therapy, of which, 78% (25/32) achieved at least 1 platelet count of at ...

6. tavalissehcp.com tavalissehcp.com/safety

TAVALISSE® (fostamatinib disodium hexahydrate) tablets THE 5-YEAR SAFETY ANALYSIS CONTINUES TO SUPPORT LONG-TERM USE OF TAVALISSE. The majority of adverse reactions observed in clinical trials were mild or moderate1.

7. ahdbonline.com ahdbonline.com/web-exclusives/fda-approvals/tavalisse-fostamatinib-disodium-hexahydrate-first-spleen-tyrosine-kinase-inhibitor-approved-for-chronic-immune-thrombocytopenia

Tavalisse (Fostamatinib Disodium Hexahydrate) First ... Fostamatinib can cause fetal harm when administered to a pregnant woman; women of reproductive potential should be advised to use effective contraception ...