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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00446095
• Other study ID #: D4300C00023
• Secondary ID: C-935788-009
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 8, 2007
• Last updated: December 17, 2014
• Start date: April 2007
• Est. completion date: October 2010

Study information

• Verified date: December 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: October 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell

Intervention

Drug:
• fostamatinib
200 mg PO BID

Locations

Country	Name	City	State
United States	Research Site	Atlanta	Georgia
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chicago	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Los Angeles	California
United States	Research Site	New York	New York
United States	Research Site	Omaha	Nebraska
United States	Research Site	Rochester	New York
United States	Research Site	Rochester	Minnesota
United States	Research Site	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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)	No
Primary	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)	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)	No
Secondary	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.	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)	No
Secondary	Overall Survival (OS)	OS: Time from date of first study drug administration to the date of death.	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)	No