Bortezomib and CHOP in Patients With Advanced Stage Aggressive T Cell or Natural Killer (NK)/T Cell Lymphomas

October 12, 2009 updated by: Samsung Medical Center

A Phase I/II Study of Bortezomib + CHOP in Patients With Advanced Stage Aggressive T Cell or NK/T Cell Lymphomas

Peripheral T-cell lymphomas (PTCLs) are neoplasias from post-thymic T-cells at different stages of differentiation and are a heterogeneous group of malignancies which present with different morphological patterns, phenotypes, and clinical presentations.

These tumours have a striking epidemiological distribution with a lower incidence in Western countries than in Asia. In Korea, PTCLs including T- or natural killer (NK)-cell lymphomas constitute approximately 25 to 35% of all non-Hodgkin's lymphomas. This incidence is quite similar to that of other Eastern Asian countries, including Japan, Hong Kong, and China.

Recent studies suggest that the T-cell phenotype is an independent significant prognostic factor, with PTCLs having one of the lowest overall survival and failure-free survival rates. Based on the investigator's experience, the overall complete remission rate was 61.2% (95% confidence interval [CI]: 48.5-72.8%) and the 5-year probability of failure-free survival was 33.5%. Median survival of all patients was 45 months (range 0-64+ months) and the 5-year probability of survival was 36.2%. Rassidakis et al. reported that expression of pro-apoptotic proteins BAX and BCL-XS, may explain the poor response of many types of PTCL to standard chemotherapy.

To overcome such poor outcome, the optimal therapy for PTCLs remains to be defined. However, because of the rarity of the disease in Western countries, only a few trials have been reported.

Bortezomib (Velcade) is a modified dipeptidyl boronic acid, and a reversible inhibitor of the chymotrypsin-like activity of the 26S proteosome. Bortezomib may induce tumor cell apoptosis or decreased bcl-2 associated drug resistance. Through phase II studies, single agent bortezomib in patients with relapsed indolent and mantle cell lymphomas showed its activity. And also preliminary data indicate that bortezomib can be safely administered in combination with dose adjusted etoposide, prednisolone, vincristine, cyclophosphamide and doxorubicin (EPOCH) chemotherapy. Therefore, it can be possible to improve the poor outcome of patients with PTCLs by a combination of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) with bortezomib as a first-line therapy.

Primary Hypothesis: Based on the clinical trials and experimental data, bortezomib can overcome pro-apoptotic proteins BAX and BCL-XS induced drug resistance.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
55

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

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

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed PTCLs and NK/T cell lymphomas excluding anaplastic lymphoma kinase (ALK)-positive anaplastic large cell T-cell lymphomas (ALCL)
  • Performance status (ECOG) ≤ 3
  • Age ≤ 65

  • At least one or more unidimensionally measurable lesion(s)

    • ≥ 2 cm by conventional computed tomography (CT)
    • ≥ 1 cm by spiral CT
    • skin lesion (photographs should be taken)
    • measurable lesion by physical examination

  • Laboratory values

    • Creatinine (Cr) < 1.5 mg% or creatinine clearance (Ccr) > 50 ml/min
    • Transaminase < 3 X upper normal value
    • Bilirubin < 2.0 mg/dl
    • Absolute neutrophil count (ANC) > 1,500/ul
    • Platelets > 75,000/ul
  • Informed consent
  • Ann Arbor stage III or IV

Exclusion Criteria:

  • Any other malignancies within the past 5 years except basal cell skin cancer or carcinoma in situ (CIS) of the cervix
  • Serious comorbid diseases
  • Pregnancy or breast feeding

Any waiver of these inclusion and exclusion criteria must be approved by the investigator and the sponsor on a case-by-case basis prior to enrolling the subject. This must be documented by both the sponsor and the investigator. No subject will be allowed to enroll in this study more than once.

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
To define the dose-limiting toxicity and maximum tolerable dose
Time Frame: Phase I
Phase I
To evaluate the overall response rate
Time Frame: Phase II
Phase II

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
To evaluate the safety and tolerability of the treatment combination
Time Frame: Phase I/II
Phase I/II
To estimate the time to progression and the duration of overall response
Time Frame: Phase II
Phase II

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Samsung Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Janssen Medical Affairs

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 7, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 7, 2006

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 11, 2006

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 14, 2009

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 12, 2009

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2005-07-021

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.

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