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

20 Participants Needed

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. ^{1 2 3 4 5}

How 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. ^{1 3 4 6 7}

Research Team

Jamie Y Hur, D.O.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility 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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Fostamatinib for the treatment of immune thrombocytopenia in adults. [2021]

2. England 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Sustained response off therapy after fostamatinib: A chronic refractory ITP case report. [2023]

5. New Zealand 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Fostamatinib for the treatment of chronic immune thrombocytopenia. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Fostamatinib in chronic immune thrombocytopenia: a profile of its use in the USA. [2022]