T Cell Lymphoma
Conditions
Keywords
T Cell Lymphoma, Lymphoma
Brief summary
Patients meeting specific inclusion and exclusion criteria will be enrolled in two stages, 19 patients in Stage 1 and 36 patients in Stage 2. Stage 2 will enroll if 4 or more patients exhibit a response at Week 8 or later in the study. All enrolled patients will be treated with Fostamatinib Disodium until disease progression. Efficacy will be assessed by tumor measurements using CT and PET (when indicated) scans and physical exam at baseline, and scans and physical exam of all disease-involved areas every 8 weeks until progression. Safety will be assessed by periodic physical exams, clinical laboratory studies, and adverse events. All patients will have a follow-up visit 30 days following last study drug treatment. Blood samples for PK assessment will be obtained from all patients enrolled in Stage 1 at protocol defined intervals.
Detailed description
Up to 61 patients (male and female) meeting the inclusion and exclusion criteria will be enrolled into this trial in two stages. All enrolled patients will be treated with R788 at 200 mg PO bid until disease progression. In the initial stage of the study, a total of 19 patients will be enrolled and treated with Fostamatinib Disodium. Should at least 4 patients exhibit a response at Week 8 or later of the study, the second stage of 36 patients will open to enrollment. Efficacy will be assessed by CT and PET scans (when indicated) and physical exam at baseline, and CT scans and physical exam of all disease-involved areas every 8 weeks until progression. Safety will be assessed by periodic physical exams, clinical laboratory studies, and adverse events. All patients will have a follow-up visit 30 days following last study drug treatment. Blood samples for PK assessment will be obtained from all patients enrolled in Stage 1 at protocol-defined intervals. Patients with accessible tumor tissue will be asked to undergo a biopsy for a fresh tissue sample for assessment of Syk activity in tumor tissue. Archived tissue samples from the initial diagnostic biopsy and the most recent biopsy for lymphoma will be obtained in the event a fresh tumor biopsy cannot be obtained. Patients who have accessible tumor tissue will be asked to consent to a second tumor biopsy at Week 8, to assess the impact of Fostamatinib Disodium treatment on the activity of Syk and its downstream markers. All baseline fresh or archived tumor tissue samples will undergo central pathology review to confirm the diagnosis of TCL.
Interventions
200 mg PO BID
Sponsors
Rigel Pharmaceuticals
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
* Patients must give written informed consent to participate in this study by signing an IRB/EC-approved Informed Consent Form (ICF) prior to admission to this study. * Males and females, 18 years of age or older. * Patients must have histologically proven T-cell lymphoma (TCL). * Patients must have documented disease progression after receiving at least one prior therapeutic regimen and must be patients for whom no known curative therapy exists.
Exclusion criteria
* Patient has a history of, or a concurrent, clinically significant illness, medical condition or laboratory abnormality that, in the investigator's opinion, could affect the conduct of the study. * Has a B-cell lymphoma, primary CNS lymphoma, or known lymphomatous involvement of the CNS, or any other NK/T-cell leukemia/lymphoma. * Has uncontrolled or poorly controlled hypertension. * Has had recent (within 1 month prior to Day 1) serious surgery or uncontrolled infectious disease. * Has any concurrent malignancy requiring treatment. * Has a known positive test for Hepatitis B surface Ag, Hepatitis C, or HIV. * Has laboratory abnormalities. * Has difficulty swallowing or malabsorption. * Has an ECOG performance status \> 2. * Has not recovered from adverse effects related to last prior therapy for lymphoma. * Has had an allotransplantation within 90 days prior to Day 1 of treatment. * Has been treated with a CYP3A4 inducer/inhibitor within 3 days prior to Day 1 of treatment or is expected to require treatment with CYP3A4 inducer/inhibitor during the course of the study. * Has received systemic steroids at a dose greater than the equivalent of 10 mg/day of prednisone within 7 days prior to Day 1 of treatment. * Has received any other investigational therapy within 5 half-lives of the agent or 2 weeks of Day 1 of treatment, whichever is longer. * Is a female of childbearing potential unless menopausal, surgically sterile, or willing to use an effective method of birth control, (oral contraceptive, mechanical barrier, long-acting hormonal agent), during the study and for 30 days thereafter. * Is pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Efficacy Endpoint for This Study is Overall Regressive Response Rate (ORRR): Proportion of Patients With a Best Response of Complete Response (CR), Partial Response (PR), or Regressive Stable Disease (RSD). | Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days) | Overall regressive response rate (ORRR) is the proportion of patients with a best response of Complete Response (CR), Partial Response (PR) (per Cheson 2007), or Regressive Stable Disease (RSD) defined as regressive disease that does not meet the criteria for partial response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate is the Proportion of Patients With Best Response of 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 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days) | Clinical benefit rate is the proportion of patients with best response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD). |
| Overall Response Rate (ORR) is the Proportion of Patients With a Best Response of Complete Response (CR) or Partial Response (PR). | Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days) | Overall response rate (ORR) is the proportion of patients with a best response of Complete Response (CR) or Partial Response (PR). |
| Duration of Overall Response is the Time From First Documentation of Complete or Partial Response, Whichever Occurs Earlier, to Discontinuation of Study Drug. | Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days) | Duration of Overall Response is the time from first documentation of Complete or Partial Response (Cheson 2007), whichever occurs earlier, to discontinuation of study drug. |
Countries
Canada, United States
Participant flow
Recruitment details
A total of 18 patients with T-Cell lymphoid malignancy were enrolled in this study from 05 March 2009 until 04 January 2010. As of 19 May 2010, no patients remain on study. All enrolled patients received at least one dose of fostamatinib. This study was conducted at 9 sites in the U.S. and Canada.
Pre-assignment details
There was a screening period of up to 28 days, after which if all inclusion/exclusion criteria were met, patients were dosed with fostamatinib treatment for a treatment period of 8 weeks. Patients could continue treatment until disease progression, toxicity or withdrawal from the study
Participants by arm
| Arm | Count |
|---|---|
| Overall Study 1-fostamatinib 200mg, BID, Oral | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ongoing | 2 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 68.5 Years STANDARD_DEVIATION 12 |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Other - Unknown | 1 Participants |
| Race/Ethnicity, Customized White | 15 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 11 / 18 |
Outcome results
Primary
The Primary Efficacy Endpoint for This Study is Overall Regressive Response Rate (ORRR): Proportion of Patients With a Best Response of Complete Response (CR), Partial Response (PR), or Regressive Stable Disease (RSD).
Overall regressive response rate (ORRR) is the proportion of patients with a best response of Complete Response (CR), Partial Response (PR) (per Cheson 2007), or Regressive Stable Disease (RSD) defined as regressive disease that does not meet the criteria for partial response.
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 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study | The Primary Efficacy Endpoint for This Study is Overall Regressive Response Rate (ORRR): Proportion of Patients With a Best Response of Complete Response (CR), Partial Response (PR), or Regressive Stable Disease (RSD). | 4 Participants |
Secondary
Clinical Benefit Rate is the Proportion of Patients With Best Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD).
Clinical benefit rate is the proportion of patients with best response of 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 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study | Clinical Benefit Rate is the Proportion of Patients With Best Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD). | 5 Participants |
Secondary
Duration of Overall Response is the Time From First Documentation of Complete or Partial Response, Whichever Occurs Earlier, to Discontinuation of Study Drug.
Duration of Overall Response is the time from first documentation of Complete or Partial Response (Cheson 2007), whichever occurs earlier, to discontinuation of study drug.
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 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall Study | Duration of Overall Response is the Time From First Documentation of Complete or Partial Response, Whichever Occurs Earlier, to Discontinuation of Study Drug. | NA Days |
Secondary
Overall Response Rate (ORR) is the Proportion of Patients With a Best Response of Complete Response (CR) or Partial Response (PR).
Overall response rate (ORR) is the proportion of patients with a best response of Complete Response (CR) or Partial Response (PR).
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 8weeks therafter or to confirm response . (Maximum duration of treatment 182 days, Maximum duration of follow-up 217 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study | Overall Response Rate (ORR) is the Proportion of Patients With a Best Response of Complete Response (CR) or Partial Response (PR). | 0 Participants |