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

January 26, 2023 updated by: Philippe Armand, MD, PhD, Dana-Farber Cancer Institute

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02215
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Drug: Gemcitabine
Other Names:
  • gemzar
Drug: Filgrastim
Other Names:
  • G-CSF
  • neupogen
Drug: Cyclophosphamide
Other Names:
  • cytoxan
Drug: Prednisone
Drug: Vincristine
Other Names:
  • oncovin
Drug: Doxorubicin
Other Names:
  • adriamycin
Drug: Plerixafor
Other Names:
  • mozobil
Procedure: Stem Cell Transplant
Other Names:
  • Stem Cell Infusion
Drug: Melphalan
Drug: Etoposide
Other Names:
  • Toposar
  • Etopophos
  • Etoposide phosphate
Drug: Busulfan
Other Names:
  • busulfex
Drug: Palifermin
Other Names:
  • KGF
  • kepivance
Procedure: Stem Cell Collection
Other Names:
  • Leukapheresis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
24-month Progression-Free Survival Rate
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.
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
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).
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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

Massachusetts General Hospital
Beth Israel Deaconess Medical Center

Investigators

  • Principal Investigator: Philippe Armand, MD, Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2013

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

December 4, 2012

First Submitted That Met QC Criteria

December 7, 2012

First Posted (Estimate)

December 10, 2012

Study Record Updates

Last Update Posted (Estimate)

January 30, 2023

Last Update Submitted That Met QC Criteria

January 26, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12-388

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on T-cell Non-Hodgkin Lymphoma

Clinical Trials on Gemcitabine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kyrgyzstan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe