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

This study has been completed.
Sponsor:
Collaborator:
Janssen Medical Affairs
Information provided by:
Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT00374699
First received: September 7, 2006
Last updated: October 12, 2009
Last verified: June 2007
  Purpose

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.


Condition Intervention Phase
Peripheral T-Cell Lymphomas
Non-Hodgkin Lymphoma
Drug: Velcade
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Bortezomib + CHOP in Patients With Advanced Stage Aggressive T Cell or NK/T Cell Lymphomas

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • To define the dose-limiting toxicity and maximum tolerable dose [ Time Frame: Phase I ] [ Designated as safety issue: Yes ]
  • To evaluate the overall response rate [ Time Frame: Phase II ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of the treatment combination [ Time Frame: Phase I/II ] [ Designated as safety issue: Yes ]
  • To estimate the time to progression and the duration of overall response [ Time Frame: Phase II ] [ Designated as safety issue: No ]

Estimated Enrollment: 55
Study Start Date: April 2006
Study Completion Date: October 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00374699

Locations
Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Sponsors and Collaborators
Samsung Medical Center
Janssen Medical Affairs
Investigators
Principal Investigator: Won Seog Kim, MD, PhD Samsung Medical Center
  More Information

No publications provided

Responsible Party: CISL (Consortium for Improving Survival of Lymphoma)
ClinicalTrials.gov Identifier: NCT00374699     History of Changes
Other Study ID Numbers: 2005-07-021
Study First Received: September 7, 2006
Last Updated: October 12, 2009
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Samsung Medical Center:
Velcade
Bortezomib
CHOP
Peripheral T-cell lymphomas(PTCLs)
natural killer (NK)-cell lymphomas

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bortezomib
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014