Back to resultsEfficacy and Safety Study of Fostamatinib Tablets to Treat B-cell Lymphoma
Primary Purpose
Lymphoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
fostamatinib
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma focused on measuring DLCL, Nodular lymphoma, Mantle cell lymphoma, Syk kinase
Eligibility Criteria
Inclusion Criteria:
- Patients must be > 18 years old.
- 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.
- 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.
- Patients must have measurable disease.
- 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:
- Patients with T-cell lymphoma or primary CNS lymphoma
- 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
- Chemotherapy within 4 weeks of Day 1 of treatment (6 weeks for mitomycin C and nitrosoureas)
- Antibody therapy or lymphoma vaccine therapy within 6 weeks of Day 1
- Radiotherapy within 2 weeks of Day 1, 4 weeks if to marrow-bearing sites (sternum, pelvis)
- Any other investigational therapy within 4 weeks of Day 1
- Significant gastrointestinal disease (Crohn's or ulcerative colitis) or major gastric or small bowel surgery
- Difficulty swallowing or malabsorption
- Patients with bone marrow impairment: Hgb < 9.0 g/dL; ANC < 1500/μL; platelets < 75,000/μL
- Patients with impairment of renal function: creatinine > 2.0 g/dL
- Patients with abnormal liver function: AST/ALT > 3x ULN (up to 5x ULN with liver involvement); bilirubin > 1.5 mg/dL
- 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)
- Patients with Karnofsky performance status < 60% (Appendix I)
- Patients whose life expectancy is < 3 months
- Patients who are known to be HIV positive
- 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
- Pregnant or nursing females
- 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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
fostamatinib
Arm Description
Outcomes
Primary Outcome Measures
Overall Response Rate as Assessed According to the"Revised Response Criteria for Malignant Lymphoma" (Cheson 2007).
Proportion of patients with Complete Response (CR) or Partial Response (PR). Revised Response Criteria for Malignant Lymphoma categorises the response of the treatment of a patient's tumour to; CR: the disappearance of all evidence of disease; PR: ≥ 50% decrease in the sum of the perpendicular diameters (SPD) of the six largest dominant nodes plus no increase in the size of other nodes and no new sites of disease; Stable Disease (SD): less than a PR but not progressive disease; Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir. Primary efficacy is based on Phase II patients only.
Clinical Benefit Rate as Assessed According to the "Revised Response Criteria for Malignant Lymphoma" (Cheson 2007).
Proportion of patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD)
Secondary Outcome Measures
Progression Free Survival (PFS)
PFS: Time from date of first study drug administration to the date of progressive disease as assessed according to the "Revised Response Criteria for Malignant Lymphoma"(Cheson 2007) or the date of death due to any cause, whichever occurred first.
Overall Survival (OS)
OS: Time from date of first study drug administration to the date of death.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00446095
Brief Title
Efficacy and Safety Study of Fostamatinib Tablets to Treat B-cell Lymphoma
Official Title
A Phase I/II Multi-Center, Open Label Trial of the Safety and Efficacy of Fostamatinib in Patients With Relapsed/Refractory B-Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
October 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rigel Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
Detailed Description
This multicenter, open-label study of fostamatinib 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, based on safety and anti-tumor activity, will be determined.
Phase II 48 additional patients, 3 groups of 16 patients each, will receive fostamatinib 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
DLCL, Nodular lymphoma, Mantle cell lymphoma, Syk kinase
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
81 (Actual)
8. Arms, Groups, and Interventions
Arm Title
fostamatinib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
fostamatinib
Other Intervention Name(s)
R935788, R788, fostamatinib
Intervention Description
200 mg PO BID
Primary Outcome Measure Information:
Title
Overall Response Rate as Assessed According to the"Revised Response Criteria for Malignant Lymphoma" (Cheson 2007).
Description
Proportion of patients with Complete Response (CR) or Partial Response (PR). Revised Response Criteria for Malignant Lymphoma categorises the response of the treatment of a patient's tumour to; CR: the disappearance of all evidence of disease; PR: ≥ 50% decrease in the sum of the perpendicular diameters (SPD) of the six largest dominant nodes plus no increase in the size of other nodes and no new sites of disease; Stable Disease (SD): less than a PR but not progressive disease; Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir. Primary efficacy is based on Phase II patients only.
Time Frame
Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response . (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days)
Title
Clinical Benefit Rate as Assessed According to the "Revised Response Criteria for Malignant Lymphoma" (Cheson 2007).
Description
Proportion of patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD)
Time Frame
Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days)
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
PFS: Time from date of first study drug administration to the date of progressive disease as assessed according to the "Revised Response Criteria for Malignant Lymphoma"(Cheson 2007) or the date of death due to any cause, whichever occurred first.
Time Frame
Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days)
Title
Overall Survival (OS)
Description
OS: Time from date of first study drug administration to the date of death.
Time Frame
Overall survival is measured from the time of first administration of study drug to death. (Maximum duration of treatment 511days, Maximum duration of follow-up 812 Days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must be > 18 years old.
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.
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.
Patients must have measurable disease.
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:
Patients with T-cell lymphoma or primary CNS lymphoma
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
Chemotherapy within 4 weeks of Day 1 of treatment (6 weeks for mitomycin C and nitrosoureas)
Antibody therapy or lymphoma vaccine therapy within 6 weeks of Day 1
Radiotherapy within 2 weeks of Day 1, 4 weeks if to marrow-bearing sites (sternum, pelvis)
Any other investigational therapy within 4 weeks of Day 1
Significant gastrointestinal disease (Crohn's or ulcerative colitis) or major gastric or small bowel surgery
Difficulty swallowing or malabsorption
Patients with bone marrow impairment: Hgb < 9.0 g/dL; ANC < 1500/μL; platelets < 75,000/μL
Patients with impairment of renal function: creatinine > 2.0 g/dL
Patients with abnormal liver function: AST/ALT > 3x ULN (up to 5x ULN with liver involvement); bilirubin > 1.5 mg/dL
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)
Patients with Karnofsky performance status < 60% (Appendix I)
Patients whose life expectancy is < 3 months
Patients who are known to be HIV positive
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
Pregnant or nursing females
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Skolnik, M.D.
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Research Site
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Research Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
59905
Country
United States
Facility Name
Research Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
19965662
Citation
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. doi: 10.1182/blood-2009-08-236471. Epub 2009 Nov 17.
Results Reference
derived
Learn more about this trial
Efficacy and Safety Study of Fostamatinib Tablets to Treat B-cell Lymphoma
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