T Cell Non-Hodgkin Lymphoma
Conditions
Keywords
T NHL, Gleevec, imatinib mesylate
Brief summary
The purpose of this research study is to evaluate the overall response rate to imatinib mesylate in participants with relapsed or refractory T cell non-Hodgkin's lymphoma. This drug has been used in chronic myeloid leukemia and information from those other research studies suggests that it may help to treat T cell non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES: Primary Objective To evaluate the overall response rate Secondary Objectives To assess the safety and tolerability To assess the duration of response To assess the progression free survival and overall survival STATISTICAL DESIGN: This trial will use a single stage design to differentiate a \>/= 25% response rate from a \</= 5% rate. If observed data is consistent with the alternative response rate of 25%, imatinib would be deemed clinically interesting and worthy of a larger phase II study.
Interventions
DRUGImatinib mesylate
Sponsors
Brigham and Women's Hospital
Novartis
Dana-Farber Cancer Institute
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
* Histologically confirmed T NHL, excluding T prolymphocytic leukemia, T lymphoblastic lymphoma, and T/NK large granular lymphocytic leukemia. * Measurable disease, defined as at least one bidimensionally measurable site of disease measuring at least 1.5cm in greatest diameter. * Failed at least one systemic chemotherapy or biologic therapy for T cell lymphoma unless it can be clearly documented that the patient can not tolerate such therapy. * 18 years of age or older * Life expectancy of greater than 3 months * ECOG Performance Status of lesser then or equal to 2 * Normal organ and marrow function as outlined in the protocol * Agree to the use of adequate contraception prior to study entry and for the duration of the study
Exclusion criteria
* Chemotherapy or radiotherapy within 4 weeks prior to entering the study * Receiving any other study agents * CNS lymphoma requiring active therapy * History of allergic reactions attributed to compounds of similar chemical or biologic composition to imatinib mesylate * Participants requiring concomitant administration of any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible * Patient previously received radiotherapy to 25% or greater of the bone marrow * Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant or lactating women * History of a different malignancy except for individuals who have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy * HIV-positive individuals on combination antiretroviral therapy * Known chronic liver disease * Major surgery within 2 weeks prior to study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Disease was evaluated radiologically at baseline, weeks 8, 16, 24 and every 12 weeks thereafter on treatment. Treatment duration was a median of 56 days (range 5-253 days). | Overall response rate is defined as the proportion of patients who achieve complete remission (CR), complete remission/unconfirmed (CRu) or partial remission (PR) based on International Workshop Criteria (IWC) \[Cheson, et al. JCO 2007\]. Per the International Working Group response criteria in lymphoma (Cheson 2007) for target lesions assessed by CT: Complete response (CR): nodes that were greater than 15 mm in greatest transverse diameter at baseline shrank to less than 15 mm in greatest transverse diameter and those that were 11-15 mm in greatest transverse diameter but had a short axis diameter greater than 10 mm had a short axis diameter less than 10mm and a transverse diameter that remained less than 15 mm; partial response (PR) was defined as a decrease in the sum of the product of the diameter of target lesions by more than 50% but not fulfilling criteria for CR. Overall response was defined as CR+PR. . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | Disease was evaluated radiologically at baseline, on treatment at weeks 8, 16, 24 and every 12 weeks thereafter, off treatment for 6 weeks or until death, whichever occurs first. Treatment duration was a median of 56 days (range 5-253 days). | Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Disease progression was assessed per International Workshop Criteria (IWC) \[Cheson, et al. JCO 2007\]. Per International Working Group response criteria in lymphoma progressive disease (PD) was defined as the appearance of new lesions; the sum of the product of the diameter (SPD) increasing ≥50% from nadir (smallest value seen during trial) in nodal target lesions overall; or, in any single nodal target lesion, a node with a short axis \> 10 mm must increase \> 50% in greatest transverse diameter or a node with short axis \<10mm must increase by at least 50% to at least 15 mm x 15 mm or have a greatest transverse diameter greater than 15 mm. |
| Overall Survival | Participants were followed long-term for survival for the earlier of 6 weeks from the end of treatment or death. Maximum follow-up was 288 days in this study cohort. | Overall survival is defined as the time from study entry to death or date last known alive. |
Countries
United States
Participant flow
Recruitment details
12 participants were enrolled between August 2008 and December 2011.
Participants by arm
| Arm | Count |
|---|---|
| Imatinib Mesylate The initial starting dose of imatinib mesylate was 400 mg by mouth once daily but intra-patient dose escalation for patients who did not achieve complete response (CR) was built in upon restaging at weeks 8 and 16. At week 8, patients with partial response (PR) or stable disease (SD) were dose escalated to 600 mg. At week 16, if these patients continued in PR or SD, dose escalated to 800 mg and for patients on 400 mg dose escalated to 600 mg. Patients who experienced disease progression could be dose escalated per MD discretion. Patients were treated as long as receiving clinical benefit and no unacceptable toxicity. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Disease Progression | 10 |
| Overall Study | New Primary Cancer | 1 |
Baseline characteristics
| Characteristic | Imatinib Mesylate |
|---|---|
| Age, Continuous | 70.7 years |
| Gender Female | 6 Participants |
| Gender Male | 6 Participants |
| International Prognostic Index (IPI) High | 1 participants |
| International Prognostic Index (IPI) High-Intermediate | 3 participants |
| International Prognostic Index (IPI) Low | 3 participants |
| International Prognostic Index (IPI) Low-Intermediate | 5 participants |
| Region of Enrollment United States | 12 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 12 |
| serious Total, serious adverse events | 5 / 12 |
Outcome results
Primary
Overall Response Rate
Overall response rate is defined as the proportion of patients who achieve complete remission (CR), complete remission/unconfirmed (CRu) or partial remission (PR) based on International Workshop Criteria (IWC) \[Cheson, et al. JCO 2007\]. Per the International Working Group response criteria in lymphoma (Cheson 2007) for target lesions assessed by CT: Complete response (CR): nodes that were greater than 15 mm in greatest transverse diameter at baseline shrank to less than 15 mm in greatest transverse diameter and those that were 11-15 mm in greatest transverse diameter but had a short axis diameter greater than 10 mm had a short axis diameter less than 10mm and a transverse diameter that remained less than 15 mm; partial response (PR) was defined as a decrease in the sum of the product of the diameter of target lesions by more than 50% but not fulfilling criteria for CR. Overall response was defined as CR+PR. .
Time frame: Disease was evaluated radiologically at baseline, weeks 8, 16, 24 and every 12 weeks thereafter on treatment. Treatment duration was a median of 56 days (range 5-253 days).
Population: The analysis dataset is comprised of disease evaluable participants. One patient was ineligible based on diagnosis of diffuse large B-cell lymphoma.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imatinib Mesylate | Overall Response Rate | 0.0 proportion of participants |
Secondary
Overall Survival
Overall survival is defined as the time from study entry to death or date last known alive.
Time frame: Participants were followed long-term for survival for the earlier of 6 weeks from the end of treatment or death. Maximum follow-up was 288 days in this study cohort.
Population: The analysis dataset is comprised of disease evaluable participants. One patient was ineligible based on diagnosis of diffuse large B-cell lymphoma.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Imatinib Mesylate | Overall Survival | 154 days |
Secondary
Progression-Free Survival
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Disease progression was assessed per International Workshop Criteria (IWC) \[Cheson, et al. JCO 2007\]. Per International Working Group response criteria in lymphoma progressive disease (PD) was defined as the appearance of new lesions; the sum of the product of the diameter (SPD) increasing ≥50% from nadir (smallest value seen during trial) in nodal target lesions overall; or, in any single nodal target lesion, a node with a short axis \> 10 mm must increase \> 50% in greatest transverse diameter or a node with short axis \<10mm must increase by at least 50% to at least 15 mm x 15 mm or have a greatest transverse diameter greater than 15 mm.
Time frame: Disease was evaluated radiologically at baseline, on treatment at weeks 8, 16, 24 and every 12 weeks thereafter, off treatment for 6 weeks or until death, whichever occurs first. Treatment duration was a median of 56 days (range 5-253 days).
Population: The analysis dataset is comprised of disease evaluable participants. One patient was ineligible based on diagnosis of diffuse large B-cell lymphoma.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Imatinib Mesylate | Progression-Free Survival | 21 days |