Brief Title
Efficacy and Safety Study of Fostamatinib Disodium Tablets to Treat T-Cell Lymphoma
Official Title
Phase II, Multicenter, Simon Two-Stage Study of Fostamatinib Disodium in Patients With Relapsed or Refractory T-Cell Lymphoma
Brief Summary
Patients meeting specific inclusion and exclusion criteria will be enrolled in two stages, 19
patients in Stage 1 and 36 patients in Stage 2. Stage 2 will enroll if 4 or more patients
exhibit a response at Week 8 or later in the study. All enrolled patients will be treated
with Fostamatinib Disodium until disease progression. Efficacy will be assessed by tumor
measurements using CT and PET (when indicated) scans and physical exam at baseline, and scans
and physical exam of all disease-involved areas every 8 weeks until progression. Safety will
be assessed by periodic physical exams, clinical laboratory studies, and adverse events. All
patients will have a follow-up visit 30 days following last study drug treatment. Blood
samples for PK assessment will be obtained from all patients enrolled in Stage 1 at protocol
defined intervals.
Detailed Description
Up to 61 patients (male and female) meeting the inclusion and exclusion criteria will be
enrolled into this trial in two stages. All enrolled patients will be treated with R788 at
200 mg PO bid until disease progression. In the initial stage of the study, a total of 19
patients will be enrolled and treated with Fostamatinib Disodium. Should at least 4 patients
exhibit a response at Week 8 or later of the study, the second stage of 36 patients will open
to enrollment. Efficacy will be assessed by CT and PET scans (when indicated) and physical
exam at baseline, and CT scans and physical exam of all disease-involved areas every 8 weeks
until progression. Safety will be assessed by periodic physical exams, clinical laboratory
studies, and adverse events. All patients will have a follow-up visit 30 days following last
study drug treatment. Blood samples for PK assessment will be obtained from all patients
enrolled in Stage 1 at protocol-defined intervals. Patients with accessible tumor tissue will
be asked to undergo a biopsy for a fresh tissue sample for assessment of Syk activity in
tumor tissue. Archived tissue samples from the initial diagnostic biopsy and the most recent
biopsy for lymphoma will be obtained in the event a fresh tumor biopsy cannot be obtained.
Patients who have accessible tumor tissue will be asked to consent to a second tumor biopsy
at Week 8, to assess the impact of Fostamatinib Disodium treatment on the activity of Syk and
its downstream markers. All baseline fresh or archived tumor tissue samples will undergo
central pathology review to confirm the diagnosis of TCL.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
The Primary Efficacy Endpoint for This Study is Overall Regressive Response Rate (ORRR): Proportion of Patients With a Best Response of Complete Response (CR), Partial Response (PR), or Regressive Stable Disease (RSD).
Secondary Outcome
Clinical Benefit Rate is the Proportion of Patients With Best Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD).
Condition
T Cell Lymphoma
Intervention
Fostamatinib Disodium
Study Arms / Comparison Groups
1
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
18
Start Date
March 2009
Completion Date
April 2010
Primary Completion Date
April 2010
Eligibility Criteria
Inclusion Criteria:
- Patients must give written informed consent to participate in this study by signing an
IRB/EC-approved Informed Consent Form (ICF) prior to admission to this study.
- Males and females, 18 years of age or older.
- Patients must have histologically proven T-cell lymphoma (TCL).
- Patients must have documented disease progression after receiving at least one prior
therapeutic regimen and must be patients for whom no known curative therapy exists.
Exclusion Criteria:
- Patient has a history of, or a concurrent, clinically significant illness, medical
condition or laboratory abnormality that, in the investigator's opinion, could affect
the conduct of the study.
- Has a B-cell lymphoma, primary CNS lymphoma, or known lymphomatous involvement of the
CNS, or any other NK/T-cell leukemia/lymphoma.
- Has uncontrolled or poorly controlled hypertension.
- Has had recent (within 1 month prior to Day 1) serious surgery or uncontrolled
infectious disease.
- Has any concurrent malignancy requiring treatment.
- Has a known positive test for Hepatitis B surface Ag, Hepatitis C, or HIV.
- Has laboratory abnormalities.
- Has difficulty swallowing or malabsorption.
- Has an ECOG performance status > 2.
- Has not recovered from adverse effects related to last prior therapy for lymphoma.
- Has had an allotransplantation within 90 days prior to Day 1 of treatment.
- Has been treated with a CYP3A4 inducer/inhibitor within 3 days prior to Day 1 of
treatment or is expected to require treatment with CYP3A4 inducer/inhibitor during the
course of the study.
- Has received systemic steroids at a dose greater than the equivalent of 10 mg/day of
prednisone within 7 days prior to Day 1 of treatment.
- Has received any other investigational therapy within 5 half-lives of the agent or 2
weeks of Day 1 of treatment, whichever is longer.
- Is a female of childbearing potential unless menopausal, surgically sterile, or
willing to use an effective method of birth control, (oral contraceptive, mechanical
barrier, long-acting hormonal agent), during the study and for 30 days thereafter.
- Is pregnant or lactating.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Jeffrey Skolnik, MD, ,
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT00798096
Organization ID
D4300C00024
Secondary IDs
C-935788-017
Responsible Party
Sponsor
Study Sponsor
Rigel Pharmaceuticals
Study Sponsor
Jeffrey Skolnik, MD, Study Director, AstraZeneca
Verification Date
August 2016