CHOEP + High Dose Therapy + Auto SCT for T-Cell Lymphoma

Study Overview
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Brief Summary
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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
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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

Official Title
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A Phase II Study of CHOEP Induction Followed by Gemcitabine/Busulfan/Melphalan Autologous Stem Cell Transplantation for Patients With Newly Diagnosed T-Cell Lymphoma

Conditions
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T-cell Non-Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Etoposide
* Drug: Prednisone
* Drug: Filgrastim
* Drug: Plerixafor
* Procedure: Stem Cell Collection
* Drug: Palifermin
* Drug: Gemcitabine
* Drug: Busulfan
* Drug: Melphalan
* Procedure: Stem Cell Transplant


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHOEP + High Dose Therapy + Auto SCT<br>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). | Drug: Cyclophosphamide<br> <br> * Other names: cytoxan;Drug: Doxorubicin<br> <br> * Other names: adriamycin;Drug: Vincristine<br> <br> * Other names: oncovin;Drug: Etoposide<br> <br> * Other names: Etoposide phosphate;Drug: Prednisone<br> <br> Drug: Filgrastim<br> <br> * Other names: G-CSF;Drug: Plerixafor<br> <br> * Other names: mozobil;Procedure: Stem Cell Collection<br> <br> * Other names: Leukapheresis;Drug: Palifermin<br> <br> * Other names: kepivance;Drug: Gemcitabine<br> <br> * Other names: gemzar;Drug: Busulfan<br> <br> * Other names: busulfex;Drug: Melphalan<br> <br> Procedure: Stem Cell Transplant<br> <br> * Other names: Stem Cell Infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T Cell lymphoma