Efficacy and Safety Study or Fostamatinib Disodium Tablets to Treat B-cell Lymphoma

This study has been completed.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00446095
First received: March 8, 2007
Last updated: August 17, 2011
Last verified: August 2011
  Purpose

Patients: B-cell lymphoma, refractory, diffuse, nodular, mantle, other Phase I : Two groups of 6 patients, escalating dose tolerability- 28 days Phase II: Three groups of 16 patients (nodular, diffuse large cell, mantle cell plus others). Oral bid dosing with highest tolerable dose until toxicity, progression, or withdrawal


Condition Intervention Phase
Lymphoma
Drug: Fostamatinib Disodium
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Multi-Center, Open Label Trial of the Safety and Efficacy of Fostamatinib Disodium in Patients With Relapsed/Refractory B-Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Overall response rate (proportion of patients with best response of complete response (CR), unconfirmed response (CRu), partial response (PR)) for each group from Phase II [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Clinical benefit rate (proportion of patients with best response of CR, CRu, PR, stable disease (SD)) for each group from Phase II [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of Fostamatinib Disodium [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Progression free survival for each Phase II group [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Overall survival for each Phase II group [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: April 2007
Study Completion Date: October 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fostamatinib Disodium Drug: Fostamatinib Disodium
200 mg PO BID
Other Name: R935788, fostamatinib

Detailed Description:

This multicenter, open-label study of Fostamatinib Disodium will take place in two phases.

Phase I Two cohorts, of 6 patients each, will be sequentially assigned to receive 200 mg (Cohort 1) and 250 mg (Cohort 2) PO bid of R788. Patients will be enrolled at 250 mg bid in Cohort 2 only if < 1/6 patients in Cohort 1 experience dose-limiting toxicity (DLT) during the initial 28-day treatment period. If 2 or more patients in Cohort 1 experience DLT during the initial 28-day treatment period, patients in Cohort 2 will receive 150 mg PO bid.

Patients who do not experience DLT or disease progression may continue treatment at the assigned dose level until disease progression, toxicity or withdrawal. Patients who experience DLT may resume treatment at a lower dose level (dose will be decreased by 50 mg) when the toxicity grade has decreased to ≤ 1. Once all patients in Phase I have completed 28 days of treatment, the optimal dose of Fostamatinib Disodium, based on safety and anti-tumor activity, will be determined.

Phase II 48 additional patients, 3 groups of 16 patients each, will receive Fostamatinib Disodium at the optimal biologic dose PO bid until tumor progression, limiting toxicity or withdrawal. Group 1 will consist of patients with diffuse large B-cell lymphoma (DLBCL), Group 2 will consist of patients with follicular lymphoma, and Group 3 will consist of patients with mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphomas, small lymphocytic lymphomas (SLL), and chronic lymphocytic leukemia (CLL).

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must be > 18 years old.
  2. Patients must be willing and able to give written informed consent by signing an IRB-approved Informed Consent Form prior to admission to this study and must fully understand the requirements of the study and be willing to comply with all study visits and assessments.
  3. Patients with relapsed/refractory B-cell malignancy, (DLBCL, follicular lymphoma, mantle cell lymphoma, MALT lymphoma, marginal zone lymphoma, CLL or SLL), who have failed at least one prior treatment regimen and for whom no standard therapy exists; patients who are intolerant of standard therapy or who are not candidates for available standard therapy may also be included.
  4. Patients must have measurable disease.
  5. Patients may be male or female. Men, if sexually active, must agree to use at least one medically acceptable form of birth control for the duration of the study and for 30 days thereafter. Sexually active women of childbearing potential must have a negative serum pregnancy test, and agree to use two independent methods of birth control for the duration of the study and for 30 days thereafter.

Exclusion Criteria:

  1. Patients with T-cell lymphoma or primary CNS lymphoma
  2. Patients with a history of malignancy other than lymphoma, except basal cell carcinoma of the skin and in situ cervical carcinoma, if < 2 years since curative treatment
  3. Chemotherapy within 4 weeks of Day 1 of treatment (6 weeks for mitomycin C and nitrosoureas)
  4. Antibody therapy or lymphoma vaccine therapy within 6 weeks of Day 1
  5. Radiotherapy within 2 weeks of Day 1, 4 weeks if to marrow-bearing sites (sternum, pelvis)
  6. Any other investigational therapy within 4 weeks of Day 1
  7. Significant gastrointestinal disease (Crohn's or ulcerative colitis) or major gastric or small bowel surgery
  8. Difficulty swallowing or malabsorption
  9. Patients with bone marrow impairment: Hgb < 9.0 g/dL; ANC < 1500/μL; platelets < 75,000/μL
  10. Patients with impairment of renal function: creatinine > 2.0 g/dL
  11. Patients with abnormal liver function: AST/ALT > 3x ULN (up to 5x ULN with liver involvement); bilirubin > 1.5 mg/dL
  12. Patients who have been treated with a CYP3A4 inducer/inhibitor within 1 week prior to Day 1 or who are expected to require treatment with CYP3A4 inducer/inhibitor during the course of the study (Appendix IV)
  13. Patients with Karnofsky performance status < 60% (Appendix I)
  14. Patients whose life expectancy is < 3 months
  15. Patients who are known to be HIV positive
  16. Patients who have a history of any other significant medical or physical condition that might impair the patient's well being or preclude full participation in the study
  17. Pregnant or nursing females
  18. Patients receiving systemic or chronic inhaled steroids, with the exception of intermittent dexamethasone for the treatment of emesis or intermittent steroid inhalers for exacerbations of asthma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00446095

Locations
United States, California
Research Site
Los Angeles, California, United States, 90095
Research Site
Stanford, California, United States, 94305
United States, Georgia
Research Site
Atlanta, Georgia, United States, 30322
United States, Illinois
Research Site
Chicago, Illinois, United States, 60612
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02115
United States, Minnesota
Research Site
Rochester, Minnesota, United States, 59905
United States, Nebraska
Research Site
Omaha, Nebraska, United States, 68198
United States, New York
Research Site
New York, New York, United States, 10065
Research Site
Rochester, New York, United States, 14642
United States, Ohio
Research Site
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Jeffrey Skolnik, M.D. AstraZeneca
  More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: MSD, AstraZeneca
ClinicalTrials.gov Identifier: NCT00446095     History of Changes
Other Study ID Numbers: D4300C00023, C-935788-009
Study First Received: March 8, 2007
Last Updated: August 17, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
DLCL
Nodular lymphoma
Mantle cell lymphoma
Syk kinase

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2014