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

Chronic GVHD Clinical Trial

Official title: A Phase II Study Using Fostamatinib to Treat Post-Hematopoietic Stem Cell Transplant Immune-Mediated Cytopenias

Status Recruiting

Clinical Trial 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.

Clinical Trial Description

Study Description:

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 improvement in anemia and/or thrombocytopenia following a 12-week treatment course. Patients who respond to the 12-week treatment course on this single arm study are eligible and have the option to enroll on the extended access trial.

Objectives:

The primary objective is to assess efficacy of fostamatinib for stable hematologic recovery during post-hematopoietic stem cell transplant immune mediated anemia and/or thrombocytopenia.

The secondary objective is to assess efficacy of fostamatinib for clinically-relevant outcomes in post-hematopoietic stem cell transplant patients.

The exploratory objective is to evaluate changes in serologic markers that may be associated with cytopenias while on treatment to identify key elements for fostamatinib response.

Endpoints:

Primary endpoints:

The proportion of subjects with hematologic recovery that is stable, defined as improvement documented in 2 consecutive available readings at least 2 weeks apart, without recent blood product transfusion support in the past 7 days.

-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

Secondary endpoints:

-Proportion of subjects who achieve objective hematologic recovery within the 12-week treatment course defined as:

--Hemoglobin >=9 g/dL (or at least >=1 g/dL above baseline) in subjects enrolled with anemia or at least >=1 g/dL above baseline in subjects with symptomatic anemia

OR

--Platelets >= 30 x 10^9/L (or at least >=10 x 10^9/L above baseline) in subjects enrolled with thrombocytopenia

OR

-- Either of the above criteria in subjects with Evans syndrome

• Average weekly requirement of transfused blood component or growth factor requirement (total units of PRBC or Platelets/week, total dose of growth factor/week) by week 12, compared to the week prior to the start of the study drug.

• Change in corticosteroid dose over time, measured by median daily weight-based prednisone-equivalent corticosteroid dose in a week, from week 1 to week 12

• Change in other immunosuppressant dose over time, measured by median daily dose of the immunosuppressant in a week, from week 1 to week 12

• Number of patients who achieved >=50% steroid dose reduction by week 12 compared to week 1

• Incidence and severity of cGVHD according to 2014 NIH Consensus Criteria, at baseline before the initiation of treatment, and at week 12

Exploratory endpoints:

• Absolute percentage change in B cell chimerism pre-treatment, vs weeks 4 and 12.

• cPRA change in the preformed HLA antibodies before and after treatment in subjects with thrombocytopenia or Evans syndrome

• Percent MFI change of preformed HLA antibodies before and after treatment. This applies for antibodies with an MFI >1,000.

• Anti-RBC alloantibody titer change in patients with hemolytic anemia before and after treatment

• Assessment of serial cytokines pre-treatment and weeks 4 and 12. Cytokines include CRP, IL-1, IL-2, IL-6, IFN gamma, TNF alpha, EPO and TPO

• Immunoglobulin level changes pre-treatment, and weeks 4 and 12.

• Absolute reticulocyte count, lactate dehydrogenase, haptoglobin changes pre-treatment, and at each biweekly study visit, in patients with anemia or Evans syndrome

• Change in the weekly rate and severity of bleeding according to the total score of the ITP-Bleeding Scale (IBLS), from week -1 (one week before the start of the study drug) to week 12, in subjects with thrombocytopenia or Evans syndrome ;

Related Conditions & MeSH terms

• Chronic GVHD
• Thrombocytopenia

• NCT number: NCT05502783
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Jamie Y Hur, D.O.
• Phone: (301) 402-2399
• Email: jamie.hur@nih.gov
• Status: Recruiting
• Phase: Phase 2
• Start date: March 10, 2023
• Completion date: April 1, 2026