Diffuse Large B-Cell Lymphoma
Conditions
Keywords
lymphoma, DLBCL, fostamatinib, Diffuse Large B-Cell Lymphoma (DLBCL)
Brief summary
This study will evaluate the effectiveness of fostamatinib (200 mg twice a day) in patients with worsening or unmanageable lymphoma with a specific type of lymphoma called Diffuse Large B-Cell Lymphoma (abbreviated as DLBCL)
Detailed description
Phase II Trial to Evaluate the Efficacy of Fostamatinib in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Interventions
DRUGFostamatinib
Phase II Trial to evaluate the efficacy of 200mg fostamatinib
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged at least 18 years of age. * Patients with relapsed or refractory diffuse large B-cell lymphoma who have previously received R-CHOP (or equivalent) chemo-immunotherapy and high dose chemotherapy with stem cell rescue, or who are ineligible for high dose therapy with stem cell rescue. * Measurable disease as defined by Cheson et al 2007 criteria. * One fresh pre-treatment excisional or core needle biopsy from suitable and accessible site. * World Health Organization (WHO) performance status 0 to 1.
Exclusion criteria
* Treatment with nitrosurea, mitomycin C, investigational agents or study drugs w/in28 days of first dose of study treatment, any other chemotherapy, immunotherapy or anticancer agents w/in 3 weeks of first dose of study treatment, previous fostamatinib. * With the exception of alopecia, any unresolved toxicities from prior therapy or surgery greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1. * Uncontrolled hypertension (defined as \>140mmHg systolic and/or \> 90 mmHG diastolic at baseline with or without antihypertensive therapy. * Evidence of tuberculosis (TB). * Inadequate boen marrow reserve.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Week 8 | Patients were assessed using the revised response criteria for malignant lymphoma (Cheson). Patients were assessed for response, with CT and FDG-PET scans at 8 weeks, then every 12 weeks until radiological progression by clinical CT. Complete response (CR) was defined as disappearance of all target and non-target lesions in the liver and spleen and all lymph node masses regressed to normal size. Partial response (PR) was defined as ≥50% reduction in sum of the product of the diameters (SPD) for measured lymph nodes, splenic and liver lesions separately compared to baseline SPD. Objective response rate (CR + PR) analysis, exact binomial test, primary analysis. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
This study was conducted in the US and UK. Patient enrolment was completed on 14 June 2013. However three patients, considered by the Investigator to still be receiving clinical benefit, continue to receive fostamatinib. A total of 102 patients were enrolled and 68 received Fostamatinib doses of 100mg or 200mg and 38 Screen Failures.
Participants by arm
| Arm | Count |
|---|---|
| 100mg BID 100mg Fostmatinib BID | 21 |
| 200mg BID 200mg Fostmatinib BID | 47 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 |
| Overall Study | Ongoing | 2 | 1 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | 100mg BID | 200mg BID | Total |
|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 12.38 | 63.9 years STANDARD_DEVIATION 12.78 | 63.6 years STANDARD_DEVIATION 12.57 |
| Sex: Female, Male Female | 9 Participants | 12 Participants | 21 Participants |
| Sex: Female, Male Male | 12 Participants | 35 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 21 | 44 / 47 |
| serious Total, serious adverse events | 3 / 21 | 12 / 47 |
Outcome results
Primary
Objective Response Rate
Patients were assessed using the revised response criteria for malignant lymphoma (Cheson). Patients were assessed for response, with CT and FDG-PET scans at 8 weeks, then every 12 weeks until radiological progression by clinical CT. Complete response (CR) was defined as disappearance of all target and non-target lesions in the liver and spleen and all lymph node masses regressed to normal size. Partial response (PR) was defined as ≥50% reduction in sum of the product of the diameters (SPD) for measured lymph nodes, splenic and liver lesions separately compared to baseline SPD. Objective response rate (CR + PR) analysis, exact binomial test, primary analysis.
Time frame: Week 8
Population: Full analysis set - all randomised patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100mg BID | Objective Response Rate | 2 Patients |
| 200mg BID | Objective Response Rate | 0 Patients |