T Cell Lymphoma
Conditions
Keywords
relapsed or refractory T cell lymphoma
Brief summary
This study will be a pilot study of sorafenib 400mg PO twice daily in refractory T-cell lymphomas including peripheral T-cell lymphoma (PTCL), angioimmunoblastic lymphadenopathy (AILD), cutaneous T cell lymphoma (CTCL), anaplastic large cell lymphoma (ALCL) and other transformed T-cell lymphomas with the primary objective of studying the biological effects of the multikinase inhibitor, sorafenib.
Detailed description
Primary objectives: • To study the biological effects of sorafenib 400mg BID on the mitogen-activated protein kinase (MAPK) pathway, specifically the inhibition of extracellular signal-regulated kinases (ERK) phosphorylation, and to correlate with clinical activity in patients with T-cell lymphoma. Secondary objectives: * To observe the clinical activity of sorafenib 400mg BID by determining response rate, and progression free survival in patients with T-cell lymphoma. Duration of response and duration of stable disease will also be measured. * To determine the tolerability of sorafenib in patients with T-cell lymphoma. Exploratory objectives: * To observe the effects of sorafenib on T-cell subsets (CD4/CD8 ratio, and Tregs), and the effects of sorafenib on the monocytoid population. * To observe the effects of sorafenib on the serum cytokine profile. * To observe the effects of sorafenib on the T-cell receptor pathway, i.e. Lck, ZAP-70, and Syk. * To observe changes in lymph node or skin morphology including tumor cell infiltrate, vasculature, and the tumor microenvironment in patients treated with sorafenib by performing serial biopsies of lymph nodes or skin.
Interventions
DRUGSorafenib
Intrapatient dose reduction to 400 mg once daily and then 400 mg every other day will be allowed depending on the type and severity of toxicity encountered provided that criteria for patient withdrawal from study treatment have not been met.
Sponsors
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Histologically confirmed T-cell lymphoma including PTCL, AITL, CTCL, ALCL (Alk+, and Alk-), and other transformed T-cell lymphomas * Age \> 18 years old * Measureable disease, as defined by the Cheson criteria * ECOG Performance Status of 0 or 1 * Life expectancy \> 12 weeks * Adequate bone marrow, liver and renal function * Patients with hemoglobin \< 8.5g/dL, or ANC 500-1000/mm3, or platelets 50,000-75,000/mm3 (Grade 3), whose cytopenias are due to bone marrow involvement by T-cell lymphoma will also be eligible
Exclusion criteria
* Prior treatment with sorafenib, or other agents with similar activity, i.e. bevacizumab, imatinib, sunitinib. * Prior treatment with allogeneic stem cell transplant * Cardiac disease: Congestive heart failure \> class II NYHA.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 29 days | Overall response rate to sorafenib. Complete response by recist criteria was complete disappearance of all tumor lesions. partial response was 30% reduction in all sites of disease. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib Sorafenib, 400 mg PO twice daily
Sorafenib: Intrapatient dose reduction to 400 mg once daily and then 400 mg every other day will be allowed depending on the type and severity of toxicity encountered provided that criteria for patient withdrawal from study treatment have not been met. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Sorafenib |
|---|---|
| Age, Customized Age | 68 years |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Overall Response Rate
Overall response rate to sorafenib. Complete response by recist criteria was complete disappearance of all tumor lesions. partial response was 30% reduction in all sites of disease.
Time frame: 29 days
Population: all patients enrolled were assessed for response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib | Overall Response Rate | 5 participants |