Using Fostamatinib to Treat Post-Hematopoietic Stem Cell Transplant Immune-mediated Cytopenias

NCT05502783 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 10000758000758-H
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Immune Mediated Thrombocytopenia; Chronic GVHD; Immune Mediated Anemia

Keywords

Allogeneic Hematopoietic Stem Cell Transplant; Graft Versus Host Disease; Spleen Tyrosine Kinase (Syk) Inhibitor

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Were Able to Maintain Hematologic Recovery

  Stable hematologic recovery (improvement documented in 2 consecutive available readings) without recent blood product transfusion support (in the past 48-72 hours). Hematologic recovery is defined as: * Hemoglobin =10 g/dL (or at least =2 g/dL above baseline) in participants enrolled with posttransplant anemia. In participants with symptomatic anemia, a hemoglobin increase of at least =2 g/dL above baseline is required OR * Platelets = 50 x 10\^9/L (or at least =20 x 10\^9/L above baseline) in participants enrolled with posttransplant thrombocytopenia OR * Both of the above criteria in participants with posttransplant Evans syndrome

  Baseline, Week 2, Week 4, Week 6, Week 8, Week 10

Secondary Outcomes (7)

• Number of Participants Who Achieve Objective Hematologic Recovery

  Up to 10 weeks

• Median Change in Requirement of Transfused Blood Component

  Baseline, Week 2, Week 4, Week 6, Week 8, Week 10

• Median Change in Requirement of Growth Factor Injections

  Baseline, Week 2, Week 4, Week 6, Week 8, Week 10

• Median Change in Requirement Corticosteroid Dose (Prednisone)

  Baseline, Week 2, Week 4, Week , Week 8, Week 10

• Median Change in Other Immunosuppressant Dose

  Baseline, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12

Study Arms (1)

Fostamatinib in Participants Post-Hematopoietic Stem Cell Transplant with Immune-Mediated Cytopenias

EXPERIMENTAL

Participants Post-Hematopoietic Stem Cell Transplant with Immune-Mediated Cytopenias will receive fostamatinib 100 mg BID by mouth for 4 weeks. On the 4-week evaluation, a) if cytopenia improves (hemoglobin =10 g/dL, platelets = 50 x 109/L), patients will continue the same dose for a total of 12 weeks, b) if refractory cytopenias persist (hemoglobin \< 10 g/dL, platelets \< 50 x 109/L), the dose will be increased to 150 mg BID. Subjects with persistent (=2 readings, 2 weeks apart) loss of hematologic response after week 5 can increase their dose to 150 mg BID until at end of the study on week 12.

Drug: fostamatinib

Interventions

fostamatinib DRUG

Participants will receive fostamatinib 100 mg BID for 4 weeks. On the 4-week evaluation, a) if cytopenia improves (hemoglobin =10 g/dL, platelets = 50 x 109/L), patients will continue the same dose for a total of 12 weeks, b) if refractory cytopenias persist (hemoglobin \< 10 g/dL, platelets \< 50 x 109/L), the dose will be increased to 150 mg BID. Subjects with persistent (=2 readings, 2 weeks apart) loss of hematologic response after week 5 can increase their dose to 150 mg BID until at end of the study on week 12.

Fostamatinib in Participants Post-Hematopoietic Stem Cell Transplant with Immune-Mediated Cytopenias

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18-75 years inclusive
• Ability to comprehend the investigational nature of the study and provide informed consent
• Female patients of reproductive potential agree to avoid pregnancy through abstinence or the use two forms of highly effective birth control during and for 1 month after the last study treatment and agree not to donate eggs during this time
• male patients of reproductive potential agree to avoid pregnancy of a partner through abstinence or the use two forms of highly effective birth control during and for 1 month after the last study treatment and agree not to donate sperm during this time.
• Diagnosis of an immune mediated cytopenia (anemia and/or thrombocytopenia) in a patient that either:
• Failed or relapsed after at least one line of therapy including steroids, IVIG, TPO mimetics, rituximab, azathioprine, cyclophosphamide, cyclosporine, tacrolimus, danazol, vincristine, ESA or splenectomy
• Or remains transfusion dependent (\>=1 transfusion(s)/2 weeks)
• Or is steroid dependent
• Subjects are \>=60 days post-allogeneic transplant with:
• Thrombocytopenia, defined as average platelets count \<30 x 10\^9/L for 3 consecutive available readings at least 2 weeks apart, after other cell lines have engrafted, with no counts \>40 x 10\^9/L unless from rescue transfusions. Subjects failed at least one line of therapy outlined above with a clinical diagnosis of immune mediated thrombocytopenia.
• Anemia, transfusion dependent, or defined as hemoglobin \<=9 g/dL for 3 consecutive available readings at least 2 weeks apart, after other cell lines have engrafted OR if hemoglobin 9-10 g/dL, subject must have symptomatic anemia or ongoing treatment for immune hemolytic anemia that have failed at least one line of therapy outlined above. Symptomatic anemia is defined as anemia with fatigue, weakness, shortness of breath, palpitations/fast heartbeat, lightheadedness, and/or chest pain, and these symptoms are attributed to anemia. Laboratory evaluation are recommended but not required for the diagnosis, such as a positive DAT, low haptoglobin \<lower limit of normal (LLN), indirect bilirubin \> upper limit of normal (ULN), or lactate dehydrogenase (LDH) \>ULN.
• Subjects must test negative for HIV, HBV, and HCV by standard serologic tests within the previous six months
• Subjects on other standard of care therapeutic regimens for GVHD or cytopenias should be on a stable dose of medication (no change \>=25%) for at least 15 days prior to enrollment.
• Patients with a history of hypertension should be maintained on a stable antihypertensive regimen and with controlled blood pressure (Systolic blood pressure \< 140 mmHg and diastolic blood pressure \<90 mmHg) for at least one week prior to enrollment.
• Peripheral blood or bone marrow T-cell chimerism \>=50% donor cells

You may not qualify if:

• Severe psychiatric illness or mental deficiency sufficient to make making informed consent impossible
• Positive pregnancy test for women of childbearing age within 1 week or being actively lactating
• Immune mediated cytopenia responsive to the standard of care treatment
• Immune mediated cytopenia due to other autoimmune causes, such as systemic lupus erythrocytosis, chronic lymphocytic leukemia
• Patients who have previously received or currently take fostamatinib post-allogeneic transplant
• Non-immune mediated cytopenias. Etiologies including, but not limited to, cytopenias due to HIV infection, lymphoproliferative disorders, myelodysplasia/acute leukemia, drug-induced thrombocytopenia, thrombotic microangiopathies, acute bleeding, consumptive coagulopathy, fever, infections leading to cytopenia, medications induced cytopenias, thrombotic microangiopathies (disseminated intravascular coagulation), splenomegaly or hemophagocytic lymphohistiophagocytosis, relapse of primary disease.
• Patients with neutropenia, defined as absolute neutrophil count \<=1.0 x 10\^9/L, will be excluded
• Uncontrolled hypertension (systolic blood pressure \>=140mmHg or diastolic blood pressure \>=90mmHg)
• ALT or AST \>=3 times the upper limit of normal, or direct bilirubin \>=2 times the upper limit of normal
• Patients who have a history of medical disorders, that in the investigator's opinion, could affect the conduct of the study or the absorption, metabolism or excretion of the study drug are excluded.
• Patients with lymphoma/chronic lymphocytic leukemia, hepatitis, or HIV associated with ITP/wAIHA
• Patients with evidence of graft rejection (based on clinical suspicion supported by BM biopsy data and/or chimerism studies and/or MLR)
• Subjects recently treated (within 30 days) with cytokine-targeting biologics (anti-TNF, IL6) or Bcell or plasma-cell depleting antibody.
• Other cancers except that for which the transplant was done \< 2 years before study entry, except non-melanoma skin cancer or carcinoma in situ of the uterine cervix or breast

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease

Interventions

fostamatinib

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Results Point of Contact

• Title: Dr. Georg Aue
• Organization: National Heart, Lung, and Blood Institute (NHLBI) at National Institutes of Health (NIH)

aueg@nhlbi.nih.gov

301.547.9490

Study Officials

• Jamie Y Hur, D.O.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2022
• First Posted: August 16, 2022
• Study Start: March 10, 2023
• Primary Completion: June 16, 2023
• Study Completion: June 16, 2023
• Last Updated: December 5, 2025
• Results First Posted: December 5, 2025

Record last verified: 2025-10

Locations

US (1)