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

March 8, 2007
August 17, 2011
April 2007
April 2010   (final data collection date for primary outcome measure)
  • 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 ]
  • 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
  • Clinical benefit rate (proportion of patients with best response of CR, CRu, PR, stable disease (SD)) for each group from Phase II
Complete list of historical versions of study NCT00446095 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Safety and tolerability of R788
  • Progression free survival for each Phase II group
  • Overall survival for each Phase II group
Not Provided
Not Provided
 
Efficacy and Safety Study or Fostamatinib Disodium Tablets to Treat B-cell Lymphoma
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

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

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).

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
Drug: Fostamatinib Disodium
200 mg PO BID
Other Name: R935788, fostamatinib
Experimental: Fostamatinib Disodium
Intervention: Drug: Fostamatinib Disodium
Friedberg JW, Sharman J, Sweetenham J, Johnston PB, Vose JM, Lacasce A, Schaefer-Cutillo J, De Vos S, Sinha R, Leonard JP, Cripe LD, Gregory SA, Sterba MP, Lowe AM, Levy R, Shipp MA. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2010 Apr 1;115(13):2578-85. Epub 2009 Nov 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
October 2010
April 2010   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00446095
D4300C00023, C-935788-009
Yes
MSD, AstraZeneca
AstraZeneca
Not Provided
Study Director: Jeffrey Skolnik, M.D. AstraZeneca
AstraZeneca
August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP