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

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

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.

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

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