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

NCT00446095 | Completed Phase 1 Results DMC

• 2 other identifiers: D4300C00023C-935788-009
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 11

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

Conditions

Lymphoma

Keywords

DLCL; Nodular lymphoma; Mantle cell lymphoma; Syk kinase

Outcome Measures

Primary Outcomes (2)

• 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)

• 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)

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  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)

• Overall Survival (OS)

  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)

Study Arms (1)

fostamatinib

EXPERIMENTAL

Drug: fostamatinib

Interventions

fostamatinib DRUG

200 mg PO BID

Also known as: R935788, R788, fostamatinib

fostamatinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigel Pharmaceuticals: lead

Study Sites (11)

Research Site

Los Angeles, California, 90095, United States

Location

Research Site

Stanford, California, 94305, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Chicago, Illinois, 60612, United States

Location

Research Site

Indianapolis, Indiana, 46202, United States

Location

Research Site

Boston, Massachusetts, 02115, United States

Location

Research Site

Rochester, Minnesota, 59905, United States

Location

Research Site

Omaha, Nebraska, 68198, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Rochester, New York, 14642, United States

Location

Research Site

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• 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.

  PMID: 19965662 DERIVED

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Interventions

fostamatinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Limitations and Caveats

This is a small, non-randomized study. Comparisons between the 3 groups cannot be reliably made and should be interpreted with caution.

Results Point of Contact

• Title: Anne-Marie Duliege, MD
• Organization: Rigel

clinicaltrials@rigel.com

650-624-1100

Study Officials

• Jeffrey Skolnik, M.D.

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2007
• First Posted: March 12, 2007
• Study Start: April 1, 2007
• Primary Completion: April 1, 2010
• Study Completion: October 1, 2010
• Last Updated: September 19, 2016
• Results First Posted: December 18, 2014

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)