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

Dana-Farber Cancer Institute

Status and phase

Terminated

Phase 2

Conditions

T-cell Non-Hodgkin Lymphoma

Treatments

Drug: Prednisone

Drug: Etoposide

Drug: Cyclophosphamide

Drug: Vincristine

Drug: Filgrastim

Drug: Busulfan

Drug: Palifermin

Drug: Melphalan

Procedure: Stem Cell Collection

Drug: Gemcitabine

Drug: Plerixafor

Drug: Doxorubicin

Procedure: Stem Cell Transplant

Study type

Interventional

Funder types

Other

Identifiers

NCT01746173

12-388

Details and patient eligibility

About

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.

Full 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

Enrollment

5 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

5 participants in 1 patient group

CHOEP + High Dose Therapy + Auto SCT

Experimental group

Description:

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).

Treatment: