Back to resultsExtension Study (Extended Access) of Syk-inhibition Using Fostamatinib to Treat Posttransplant Immune-mediated Cytopenias
Primary Purpose
Immune Mediated Anemia, Immune Mediated Thrombocytopenia, Chronic GVHD
Status
Enrolling by invitation
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
fostamatinib
Sponsored by
About this trial
This is an interventional treatment trial for Immune Mediated Anemia focused on measuring Allogeneic Hematopoietic Stem Cell Transplant, Graft Versus Host Disease, Spleen Tyrosine Kinase (Syk) Inhibitor
Eligibility Criteria
- INCLUSION CRITERIA:
Subjects who were enrolled on phase II trial of fostamatinib and deemed responders at the time of rollover to the extended access trial which is defined as:
- Hemoglobin >= 9 g/dL (or at least >= 1 g/dL above baseline) in subjects enrolled with posttransplant anemia without transfusion support, at least once during the 12-week phase II trial.
OR
--Platelets >= 30 X 10^9/L (or at least >= 10 X 10^9/L above baseline) without transfusion support, at least once during the 12-week phase II trial, in subjects enrolled with posttransplant thrombocytopenia
OR
--Either of the above criteria in subjects with posttransplant Evan s syndrome
- Completed the end of study visit (week 12) on the initial protocol (A Phase II Study of Syk-inhibition using Fostamatinib to treat Post-Transplant Immune-mediated Cytopenias).
- 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.
EXCLUSION CRITERIA:
- 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
- Uncontrolled hypertension (systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg)
- ALT or AST >3 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 evidence of graft rejection (based on clinical suspicion supported by BM biopsy data and/or chimerism studies and/or MLR)
- Neutropenia, defined as absolute neutrophil count <= 1.0 X 10^9/L
- 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.
Sites / Locations
- National Institutes of Health Clinical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Fostamatinib Arm
Arm Description
The subjects will receive oral fostamatinib daily for up to 2 years.
Outcomes
Primary Outcome Measures
Proportion of subjects who are able to maintain hematologic recovery
Proportion of subjects who are able to maintain hematologic recovery (as defined below) by the end of 12 weeks on the extended access trial (total of 24 weeks fostamatinib treatment). Hematologic recovery is defined as: Hemoglobin >=10 g/dL (or at least >=2 g/dL above baseline) in subjects enrolled with post-transplant anemia. In subjects with symptomatic anemia, a hemoglobin increase of at least >=2 g/dL above baseline is required OR Platelets >= 50 x 109/L (or at least =20 x 10^9/L above baseline) in subjects enrolled with post-transplant thrombocytopenia OR Both of the above criteria in subjects with post-transplant Evan s syndrome
Secondary Outcome Measures
Proportion of subjects who are able to taper off fostamatinib by >33% while maintaining hematologic recovery
Hematologic recovery is defined as: Hemoglobin >=10 g/dL (or at least >=2 g/dL above baseline) in subjects enrolled with post-transplant anemia. In subjects 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 subjects enrolled with post-transplant thrombocytopenia OR Both of the above criteria in subjects with post-transplant Evan s syndrome
Change in the dose of other immunosuppressive agents
Change in the dose of other immunosuppressive agents in the total 24 weeks on fostamatinib, measured by median daily dose of the immunosuppressant in a week, from week 1 to week 24.
Proportion of subjects who are able to completely taper off fostamatinib while maintaining hematologic recovery
Hematologic recovery is defined as: Hemoglobin >=10 g/dL (or at least >=2 g/dL above baseline) in subjects enrolled with post-transplant anemia. In subjects 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 subjects enrolled with post-transplant thrombocytopenia OR Both of the above criteria in subjects with post-transplant Evan s syndrome
Change in corticosteroid dose
Change in corticosteroid dose in the total 24 weeks on fostamatinib, measured by median daily weight-based prednisone-equivalent corticosteroid dose from week 1 to week 24.
Full Information
NCT ID
NCT05509582
First Posted
August 19, 2022
Last Updated
October 24, 2023
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT05509582
Brief Title
Extension Study (Extended Access) of Syk-inhibition Using Fostamatinib to Treat Posttransplant Immune-mediated Cytopenias
Official Title
Extension Study (Extended Access) of Syk-inhibition Using Fostamatinib to Treat Post-Transplant Immune-mediated Cytopenias
Study Type
Interventional
2. Study Status
Record Verification Date
July 28, 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
October 30, 2023 (Anticipated)
Primary Completion Date
December 1, 2028 (Anticipated)
Study Completion Date
December 1, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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. Up to 20% of people who have blood stem cell transplants develop cytopenias, which 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 evaluate the long-term effects of a study drug (fostamatinib) in people with cytopenia after a blood stem cell transplant.
Eligibility:
People who responded well to fostamatinib in an earlier study.
Design:
Participants will be screened. They will have a physical exam and blood tests.
Fostamatinib is an oral tablet taken by mouth. Participants will take the pills at the same dose and frequency as they did during the previous study. They will take the pills for up to 21 months. The dosage of the drug may be reduced over time if their blood cell levels are stable.
Participants will have a medical assessment every month. This can be with their local doctor or at the NIH clinic.
Participants will have blood tests every 3 months.
Participants will have a follow-up visit after they stop taking the drug. Their vital signs will be taken, and they will have blood drawn. They will answer questions about their health.
Detailed Description
Study Description:
This is an extension trial of a phase II study which is designed to evaluate the long-term safety and efficacy of fostamatinib in the treatment of post-transplant cytopenias as assessed by hematologic improvement in anemia and/or thrombocytopenia following an additional 12-84 weeks of treatment on the initial phase II trial. The subjects who are deemed responders to the initial 12-week treatment, will be candidates to enroll onto the extension trial for up to 2 years of treatment.
Objectives:
The primary objective is to evaluate the efficacy for the use of fostamatinib in subjects with post-transplant anemia and/or thrombocytopenia at the end of total 24 weeks of treatment.
The secondary objectives are to evaluate the long-term efficacy of subjects on fostamatinib while weaning off fostamatinib treatment either partially or completely.
Endpoints:
The primary endpoint is:
-Proportion of subjects who are able to maintain hematologic recovery (as defined below) by the end of 12 weeks on the extended access trial (total of 24 weeks fostamatinib treatment).
Hematologic recovery is defined as:
-Hemoglobin >= 10 g/dL (or at least >= 2 g/dL above baseline) in subjects enrolled with posttransplant anemia. In subjects 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 subjects enrolled with posttransplant thrombocytopenia
OR
-Both of the above criteria in subjects with posttransplant Evans syndrome
The secondary endpoints:
Proportion of subjects who are able to taper off fostamatinib by >33% while maintaining hematologic recovery as outlined above at the end of the treatment.
Proportion of subjects who are able to completely taper off fostamatinib while maintaining hematologic recovery as outlined above at the end of the treatment.
Change in corticosteroid dose in the total 24 weeks on fostamatinib, measured by median daily weight-based prednisone-equivalent corticosteroid dose in a week, from week 1 to week 24
Change in the dose of other immunosuppressive agents in the total 24 weeks on fostamatinib, measured by median daily dose of the immunosuppressant in a week, from week 1 to week 24
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immune Mediated Anemia, Immune Mediated Thrombocytopenia, Chronic GVHD
Keywords
Allogeneic Hematopoietic Stem Cell Transplant, Graft Versus Host Disease, Spleen Tyrosine Kinase (Syk) Inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Fostamatinib Arm
Arm Type
Experimental
Arm Description
The subjects will receive oral fostamatinib daily for up to 2 years.
Intervention Type
Drug
Intervention Name(s)
fostamatinib
Intervention Description
Subjects will receive fostamatinib at the same dose as the dose they receive at the time of rollover. The dose could be reduced to 100mg daily, 150 mg daily, 100 mg twice a day if a dose-limiting adverse event occurred. After the initial 12 weeks on the extended access (total of 24 weeks of treatment), subjects will have the option to start tapering fostamatinib if they are maintaining hematologic recovery. Subjects with persistent (=2 readings, 2 weeks apart) loss of hematologic response, defined as Hb<9g/dL and/or PLT< 30 X 10^9/L can increase their dose to next higher dose. Once count stabilization again occurs, a slow dose reduction to next lowest dose (100mg or 150mg) can be performed to identify the lowest dose necessary to keep counts over these thresholds.
Primary Outcome Measure Information:
Title
Proportion of subjects who are able to maintain hematologic recovery
Description
Proportion of subjects who are able to maintain hematologic recovery (as defined below) by the end of 12 weeks on the extended access trial (total of 24 weeks fostamatinib treatment). Hematologic recovery is defined as: Hemoglobin >=10 g/dL (or at least >=2 g/dL above baseline) in subjects enrolled with post-transplant anemia. In subjects with symptomatic anemia, a hemoglobin increase of at least >=2 g/dL above baseline is required OR Platelets >= 50 x 109/L (or at least =20 x 10^9/L above baseline) in subjects enrolled with post-transplant thrombocytopenia OR Both of the above criteria in subjects with post-transplant Evan s syndrome
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Proportion of subjects who are able to taper off fostamatinib by >33% while maintaining hematologic recovery
Description
Hematologic recovery is defined as: Hemoglobin >=10 g/dL (or at least >=2 g/dL above baseline) in subjects enrolled with post-transplant anemia. In subjects 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 subjects enrolled with post-transplant thrombocytopenia OR Both of the above criteria in subjects with post-transplant Evan s syndrome
Time Frame
106 weeks
Title
Change in the dose of other immunosuppressive agents
Description
Change in the dose of other immunosuppressive agents in the total 24 weeks on fostamatinib, measured by median daily dose of the immunosuppressant in a week, from week 1 to week 24.
Time Frame
12 weeks
Title
Proportion of subjects who are able to completely taper off fostamatinib while maintaining hematologic recovery
Description
Hematologic recovery is defined as: Hemoglobin >=10 g/dL (or at least >=2 g/dL above baseline) in subjects enrolled with post-transplant anemia. In subjects 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 subjects enrolled with post-transplant thrombocytopenia OR Both of the above criteria in subjects with post-transplant Evan s syndrome
Time Frame
106 weeks
Title
Change in corticosteroid dose
Description
Change in corticosteroid dose in the total 24 weeks on fostamatinib, measured by median daily weight-based prednisone-equivalent corticosteroid dose from week 1 to week 24.
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA:
Subjects who were enrolled on phase II trial of fostamatinib and deemed responders at the time of rollover to the extended access trial which is defined as:
Hemoglobin >= 9 g/dL (or at least >= 1 g/dL above baseline) in subjects enrolled with posttransplant anemia without transfusion support, at least once during the 12-week phase II trial.
OR
--Platelets >= 30 X 10^9/L (or at least >= 10 X 10^9/L above baseline) without transfusion support, at least once during the 12-week phase II trial, in subjects enrolled with posttransplant thrombocytopenia
OR
--Either of the above criteria in subjects with posttransplant Evans syndrome
Completed the end of study visit (week 12) on the initial protocol (A Phase II Study of Syk-inhibition using Fostamatinib to treat Post-Transplant Immune-mediated Cytopenias).
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.
EXCLUSION CRITERIA:
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
Uncontrolled hypertension (systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg)
ALT or AST >3 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 evidence of graft rejection (based on clinical suspicion supported by BM biopsy data and/or chimerism studies and/or MLR)
Neutropenia, defined as absolute neutrophil count <= 1.0 X 10^9/L
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jamie Y Hur, D.O.
Organizational Affiliation
National Heart, Lung, and Blood Institute (NHLBI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
12. IPD Sharing Statement
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_000760-H.html
Description
NIH Clinical Center Detailed Web Page
Learn more about this trial
Extension Study (Extended Access) of Syk-inhibition Using Fostamatinib to Treat Posttransplant Immune-mediated Cytopenias
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