Efficacy and Safety Study of Fostamatinib Disodium Tablets to Treat T-Cell Lymphoma

Phase II, Multicenter, Simon Two-Stage Study of Fostamatinib Disodium in Patients With Relapsed or Refractory T-Cell Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: T Cell Lymphoma
• Intervention / Treatment: Drug: Fostamatinib Disodium

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Research Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
• United States
  • California
    • San Francisco, California, United States, 94143
      • Research Site
    • Stanford, California, United States, 94305
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Research Site
  • New York
    • New York, New York, United States, 10021
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Fostamatinib Disodium; 200 mg PO BID; Other Names: Code Designation: R935788 Sodium Hexahydrate; USAN Name: Fostamatinib Disodium; CAS No.: 914295-16-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Overall regressive response rate (ORRR) is the proportion of patients with a best response of Complete Response (CR), Partial Response (PR) (per Cheson 2007), or Regressive Stable Disease (RSD) defined as regressive disease that does not meet the criteria for partial response.	Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate is the Proportion of Patients With Best Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD).	Clinical benefit rate is the proportion of patients with best response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD).	Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days)
Overall Response Rate (ORR) is the Proportion of Patients With a Best Response of Complete Response (CR) or Partial Response (PR).	Overall response rate (ORR) is the proportion of patients with a best response of Complete Response (CR) or Partial Response (PR).	Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days)
Duration of Overall Response is the Time From First Documentation of Complete or Partial Response, Whichever Occurs Earlier, to Discontinuation of Study Drug.	Duration of Overall Response is the time from first documentation of Complete or Partial Response (Cheson 2007), whichever occurs earlier, to discontinuation of study drug.	Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days)

Collaborators and Investigators

• Sponsor: Rigel Pharmaceuticals
• Investigators: Study Director: Jeffrey Skolnik, MD, AstraZeneca

Publications and helpful links

Helpful Links

• D4300C00024 Clinical Study Report

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: November 21, 2008
• First Submitted That Met QC Criteria: November 24, 2008
• First Posted (Estimate): November 25, 2008

Study Record Updates

• Last Update Posted (Estimate): September 19, 2016
• Last Update Submitted That Met QC Criteria: August 9, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Lymphoma; T Cell Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
• Other Study ID Numbers: D4300C00024; C-935788-017 (Other Identifier: Rigel Pharmaceuticals)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO