T-cell Non-Hodgkin Lymphoma
Conditions
Keywords
T Cell lymphoma
Brief summary
The current standard of care for the frontline treatment of peripheral T-cell lymphomas (PTCL) is induction chemotherapy followed by autologous stem cell transplantation (ASCT). However, many patients are unable to get to ASCT or relapse after ASCT, with a poor prognosis. Recently, a novel ASCT conditioning regimen of gemcitabine, busulfan and melphalan (Gem/Bu/Mel) has been reported to lead to favorable outcomes in this disease. We therefore designed a frontline regimen of CHOEP induction followed by Gem/Bu/Mel ASCT, and report the results of a phase 2 study of this regimen in patients with PTCL.
Detailed description
Objectives: Primary * To estimate the proportion of patients alive and progression-free at 24 months after beginning induction therapy Secondary * To estimate the response rate (complete remission (CR) and partial remission (PR)) after CHOEP x 6 and after Gem/Bu/Mel ASCT * To estimate overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) * To estimate the toxicity (grade 3 and above) * To estimate the rate of successful stem cell mobilization after CHOEP in responding patients * To estimate the proportion of patients who can successfully complete the entire treatment regimen * To estimate the time to engraftment of neutrophil and platelet engraftment after ASCT * To determine whether tumor DNA can be detected in peripheral blood of patients before therapy * To evaluate the changes and prognostic relevance in detectable tumor DNA in peripheral blood after induction chemotherapy (CHOEP) and after Gem/Bu/Mel ASCT
Interventions
DRUGCyclophosphamide
DRUGDoxorubicin
DRUGVincristine
DRUGEtoposide
DRUGPrednisone
DRUGFilgrastim
DRUGPlerixafor
PROCEDUREStem Cell Collection
DRUGPalifermin
DRUGGemcitabine
DRUGBusulfan
DRUGMelphalan
PROCEDUREStem Cell Transplant
Sponsors
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of T-Cell lymphoma with mandatory pathologic review at Brigham and Women's Hospital or Massachusetts General Hospital * Measurable disease * Candidate for Autologous Stem Cell Transplant
Exclusion criteria
* Prior anti-lymphoma chemotherapy (except steroids/radiotherapy for urgent palliation, one prior cycle of CHOP or up to 2 prior cycles of CHOEP) * Pregnant or breastfeeding * Alk-positive ACL * Significant neuropathy precluding vincristine administration * Known hypersensitivity to any of the agents used in the treatment * Uncontrolled intercurrent illness * Receiving other investigational agents * History of a different malignancy except if disease free for at least 5 years or have cervical cancer in situ or basal cell/squamous cell carcinoma of the skin * HIV positive on anti-retroviral therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-month Progression-Free Survival Rate | Disease was re-staged at cycles 3 and 6 during induction, at day 100 post-ASCT, and in long-term follow-up at months 12, 18, 24 and 36. All patients were evaluable up to month 24. | 24-month progression-free survival rate is defined as the proportion of patients remaining alive and progression-free at 24 months from start of induction therapy. Disease progression was assessed using a combination of CT scans and PET scans. Progression was categorized according to standard lymphoma response criteria, specifically the Revised Response Criteria (Cheson 2007). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Induction Response | Disease was re-staged at cycles 3 and 6 during induction. Median duration of induction therapy in this study cohort was 6 cycles/18 weeks (range 2-6 cycles). | Induction response is the defined as the proportion of patients who achieve complete remission (CR) or partial remission (PR) during 6 cycles of induction therapy. Response was assessed was using a combination of CT scans and PET scans. Partial and complete response were categorized according to standard lymphoma response criteria, specifically the Revised Response Criteria (Cheson 2007). Given the cycle length of 3 weeks, induction duration per protocol was 18 weeks. |
Countries
United States
Participant flow
Recruitment details
5 patients were enrolled between July 2013 and January 2014.
Participants by arm
| Arm | Count |
|---|---|
| CHOEP + High Dose Therapy + Auto SCT Patients received 6 cycles of induction chemotherapy: Cyclophosphamide, Doxorubicin, Vincristine, Etoposide and Prednisone (CHOEP) (5 if previously received 1 cycle of CHOP). CHOP was given at standard doses, with a dose of etoposide of 100 mg/m2 intravenously (IV) or 200 mg/m2 orally added on days 1-3 of each cycle. Patients who did not achieve a partial (PR) or complete (CR) remission at restaging after either 3 or 6 cycles were taken off study. Responders after 6 cycles had stem cell (SC) mobilization using filgrastim and plerixafor (if necessary) within 4 weeks of the end of induction. SC mobilization, harvesting, and reinfusion were performed per standard institutional protocol. A minimum collection of 2x106 CD34+ cells/kg was required to proceed to autologous stem cell transplant. Conditioning was comprised of gemcitabine 2700 mg/m2 on days -8 and -3, IV busulfan 105 mg/m2 days -8 to -5, and melphalan 60 mg/m2 given daily on days -3 and -2 (per MD Andersen protocol). | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease Progression | 2 |
Baseline characteristics
| Characteristic | CHOEP + High Dose Therapy + Auto SCT |
|---|---|
| Age, Continuous | 55 years |
| Region of Enrollment United States | 5 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
| Stage Stage I | 1 Participants |
| Stage Stage II | 0 Participants |
| Stage Stage III | 2 Participants |
| Stage Stage IV | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 4 / 5 |
Outcome results
Primary
24-month Progression-Free Survival Rate
24-month progression-free survival rate is defined as the proportion of patients remaining alive and progression-free at 24 months from start of induction therapy. Disease progression was assessed using a combination of CT scans and PET scans. Progression was categorized according to standard lymphoma response criteria, specifically the Revised Response Criteria (Cheson 2007).
Time frame: Disease was re-staged at cycles 3 and 6 during induction, at day 100 post-ASCT, and in long-term follow-up at months 12, 18, 24 and 36. All patients were evaluable up to month 24.
Population: The analysis dataset is comprised all enrolled patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CHOEP + High Dose Therapy + Auto SCT | 24-month Progression-Free Survival Rate | 0.0 proportion of patients |
Secondary
Induction Response
Induction response is the defined as the proportion of patients who achieve complete remission (CR) or partial remission (PR) during 6 cycles of induction therapy. Response was assessed was using a combination of CT scans and PET scans. Partial and complete response were categorized according to standard lymphoma response criteria, specifically the Revised Response Criteria (Cheson 2007). Given the cycle length of 3 weeks, induction duration per protocol was 18 weeks.
Time frame: Disease was re-staged at cycles 3 and 6 during induction. Median duration of induction therapy in this study cohort was 6 cycles/18 weeks (range 2-6 cycles).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CHOEP + High Dose Therapy + Auto SCT | Induction Response | .60 proportion of patients |