Evaluation of Fostamatinib in Patients With cGVHD After Allogeneic Stem Cell Transplant

NCT02611063 | Completed Phase 1

• 1 other identifier: Pro00064227
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether fostamatinib, a drug that blocks activated B cells will be effective in preventing and treating chronic graft vs host disease (cGVHD) after allogeneic stem cell transplant. Activated B cells may play a role in development of cGVHD. Inhibiting the B cell activation using fostamatinib after allogeneic stem cell transplant may prevent the development of cGVHD.

Conditions

Hematological Malignancies

Keywords

allogeneic stem cell transplant

Outcome Measures

Primary Outcomes (1)

• Evaluate maximum tolerated dose of fostamatinib delivered following allogenic transplantation

  three dose levels are considered: 100 mg qd, 150 mg qd, 100 mg bid dose limiting toxicity is any of the following 1. Grade \> or = II aGVHD of the gut or liver or Grade III aGVHD of the skin lasting \> 7 days and related to the agent 2. Grade 3 toxicity from the agent in the cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary or neurologic categories that lasts \> 5 days 3. fostamatinib related mortality (TRM) 4. absolute neutrophil count (ANC) of Grade 3 or 4 plus fever attributable to the agent 5. ANC\<0.5 x 10e9/L for \>5 days and attributable to the agent 6. platelet \< 25 x 10e 9/L and attributable to the agent

  day 60 after fostamatinib initiation

Secondary Outcomes (5)

• Incidence of chronic graft vs host disease (cGVHD)

  one and two years when fostamatinib administered after allogeneic HCT

• Incidence of relapse of chronic graft vs host disease (cGVHD)

  one and two years when fostamatinib administered after allogeneic HCT

• B-cell activation rate

  two years

• B-cell death rate

  two years

• Number of B-cells

  two years

Study Arms (1)

fostamatinib

EXPERIMENTAL

Subjects will receive fostamatinib 100 mg qd, 150 mg qd, or 100 mg bid with dosage determined by the modified continual reassessment method. The treatment period begins at baseline 90 days after transplant and continues for up to 1 year after transplant. In patients with steroid-refractory cGVHD who are also included on this study, these subjects also receive fostamatinib 100mg qd, 150mg qd, or 100mg bid dosage determined by the modified continual reassessment method.

Drug: fostamatinib

Interventions

fostamatinib DRUG

100mg qd, 150mg qd, or 100mg bid

fostamatinib

Eligibility Criteria

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

You may qualify if:

• Patients who have undergone allogeneic stem cell transplantation for the treatment of any hematological malignancy are eligible. Transplant must have occurred 90 days before the start of study drug.
• Peripheral blood stem cells must have been used as the stem cell source.
• Patients must have received transplantation from adult donors (both related and unrelated) who are Human Leukocyte Antigen (HLA) matched or mismatched at 1 locus (5/6) or are mismatched at one allele (3/6). Class I and II typing is to be performed by standard methods at our institution.
• Complete remission of hematological malignancy prior to transplantation. All patients must have undergone appropriate staging for their malignancy prior to transplantation including bone marrow aspirate/biopsy and radiographic scanning if indicated.
• Patients who have undergone a non-myeloablative stem cell transplant must have \> 65% donor lymphoid hematopoiesis within 30 days of study enrollment.
• Patient age greater than 18 years of age.
• ECOG performance status 0-2 or Karnofsky Performance Status (KPS) \> 60.
• Must be able to tolerate routine oral posaconazole or voriconazole as fungal prophylaxis therapy.
• Written informed consent.

You may not qualify if:

• Recipients of allogeneic stem cell transplantation using a single or multiple umbilical cord blood units or using bone marrow.
• Participation in a clinical trial evaluating another preventative strategy for chronic GVHD or ongoing participation in a clinical trial for therapy of acute GVHD. Prior completion of experimental therapy for acute GVHD is permissible if the experimental agent was used \> 14 days prior to enrollment.
• Evidence of relapsed hematologic malignancy based on routine restaging studies.
• Any evidence of ongoing gastrointestinal or hepatic acute GVHD or evidence of greater than ongoing Stage I cutaneous acute GVHD at time of enrollment. Ongoing, tapering therapy for resolved acute GVHD is permissible.
• Patients with GVHD with chronic features diagnosed prior to day +60 or prior to enrollment are ineligible.
• Patients may have received no more than one Donor Lymphocyte Infusion (DLI), DLI must have been administered \> 6 weeks prior to enrollment on study, and no plans for a DLI in the upcoming 30 days.
• Any major cardiovascular even within 6 months of study initiation, including but not limited to myocardial infarction, unstable angina, cerebrovascular accident, pulmonary embolism, heart failure uncontrolled by medications or New York Heart Association Class III or IV heart failure.
• Uncontrolled or poorly controlled hypertension, defined as systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg, whether or not the subject is receiving anti-hypertensive treatment. Subjects may be rescreened if the blood pressure is successfully and promptly controlled within 5 days using conventional anti-hypertensive therapy to achieve optimal blood pressure control (\<140/90 mmHg).
• Active hemolytic anemia.
• History of arterial or venous thrombosis (unless a single episode of venous thrombosis \> 1 year prior to study initiation).
• Liver function test abnormalities including ALT or AST \> 3.0x ULN; total bilirubin \> 1.5x ULN; alkaline phosphatase \> 2.5 x ULN
• Neutrophil count \< 1.5 x 10e9/L or platelet count \< 75 x10e9/L
• Pregnancy or lactation.

Sponsors & Collaborators

• Stefanie Sarantopoulos, MD, PhD.: lead

Study Sites (1)

Duke University of Medicine

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

fostamatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Stefanie Sarantopoulos, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: November 16, 2015
• First Posted: November 20, 2015
• Study Start: January 1, 2016
• Primary Completion: February 1, 2021
• Study Completion: February 22, 2022
• Last Updated: March 17, 2023

Record last verified: 2023-03

Locations

US (1)