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Gemcitabine and Bortezomib in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), July 2009
First Received: February 9, 2006   Last Updated: July 7, 2009   History of Changes
Sponsor: Robert H. Lurie Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00290706
  Purpose

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with bortezomib may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with gemcitabine and to see how well they work in treating patients with relapsed or refractory B-cell or T-cell non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Drug: bortezomib
Drug: gemcitabine hydrochloride
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase I/II Trial of Combination Bortezomib (VELCADE®) and Gemcitabine Therapy for Patients With Relapsed or Refractory Aggressive B- and T-Cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate (complete and partial) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to treatment failure [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 37
Study Start Date: September 2005
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate (complete and partial remission) in patients with relapsed or refractory aggressive B- or T-cell non-Hodgkin's lymphoma treated with gemcitabine hydrochloride and bortezomib.
  • Determine the maximum tolerated dose of bortezomib when administered with gemcitabine hydrochloride in these patients.

Secondary

  • Determine the time to treatment failure, duration of response, and overall survival of patients treated with this regimen.
  • Determine the safety and tolerability of this regimen in these patients.

OUTLINE: This is a phase I, dose-escalation study of bortezomib followed by a phase II, open-label study.

  • Phase I: Patients receive gemcitabine hydrochloride IV over 30 minutes and bortezomib IV over 3-5 seconds on days 1 and 8. Treatment repeats every 21 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity (DLT) OR the dose that at which 2 of 6 patients experience DLT.

  • Phase II: Patients receive gemcitabine hydrochloride and bortezomib as in phase I at the MTD.

After completion of study therapy, patients are followed periodically for 3 years.

PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of B- or T-cell non-Hodgkin's lymphoma (NHL)

    • Intermediate histology B-cell NHL, including any of the following:

      • Diffuse large B-cell lymphoma
      • Transformed large cell lymphoma
    • Any T-cell NHL histology
    • Cutaneous T-cell lymphoma (CTCL) or mycosis fungoides (MF) allowed
  • Relapsed or refractory disease, defined as disease progressed after prior complete remission (CR), partial remission (PR), or stable disease (SD) to last therapy OR failure to achieve CR, PR, or SD after completion of last therapy
  • Must have received 1-3 prior therapeutic regimens

    • Cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP) AND cyclophosphamide, vincristine, and prednisone (CVP) OR CHOP with rituximab (CHOP-R) AND CVP with rituximab (CVP-R) is considered 1 regimen
    • Monoclonal antibody (e.g., rituximab) given as maintenance therapy is considered 1 regimen
    • Salvage chemotherapy followed by an autologous stem cell transplant is considered 1 regimen
    • No more than 7 prior therapeutic regimens for patients with CTCL or MF
  • No mantle cell lymphoma

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 3 months
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

    • At least 50,000/mm^3 if documented bone marrow involvement
  • Hemoglobin ≥ 8.0 g/dL
  • AST and ALT ≤ 3 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 3 times ULN
  • Bilirubin ≤ 2 times ULN
  • Creatinine ≤ 2.0 mg/dL
  • No known history of HIV infection
  • No other active infection
  • No uncontrolled hypertension
  • No peripheral neuropathy ≥ grade 2 within the past 2 weeks
  • No myocardial infarction within the past 6 months
  • No New York Heart Association class III or IV heart failure
  • No uncontrolled angina
  • No severe uncontrolled ventricular arrhythmias
  • No acute ischemia or active conduction system abnormalities by ECG
  • No hypersensitivity to bortezomib, boron, or mannitol
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier-method contraception
  • No serious medical or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

  • Prior autologous and/or allogeneic stem cell transplantation allowed
  • More than 3 weeks since prior chemotherapy, radiotherapy, or immunotherapy
  • More than 3 weeks since prior systemic biologic anticancer therapy
  • More than 3 weeks since prior systemic corticosteroids (e.g., oral prednisone > 10 mg per day)
  • More than 2 weeks since prior investigational drug
  • No prior bortezomib or gemcitabine hydrochloride
  • No other concurrent systemic cytotoxic chemotherapy or investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00290706

Locations
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University Recruiting
Chicago, Illinois, United States, 60611-3013
Contact: Clinical Trials Office - Robert H. Lurie Comprehensive Cancer     312-695-1301     cancer@northwestern.edu    
University of Chicago Cancer Research Center Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Sonali M. Smith, MD     773-834-2895     smsmith@medicine.bsd.uchicago.edu    
Veterans Affairs Medical Center - Lakeside Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Andrew M. Evens, DO, MS     312-695-4537     a-evens@northwestern.edu    
United States, New Jersey
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Clinical Trials Office - Cancer Institute of New Jersey     732-235-8675        
United States, New York
SUNY Downstate Medical Center Recruiting
Brooklyn, New York, United States, 11203
Contact: Olcay Batuman, MD     718-270-2785     obatuman@downstate.edu    
Sponsors and Collaborators
Robert H. Lurie Cancer Center
Investigators
Principal Investigator: Andrew M. Evens, DO, MS Robert H. Lurie Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Robert H. Lurie Comprehensive Cancer Center at Northwestern University ( Andrew M. Evens )
Study ID Numbers: CDR0000456477, NU-04H4, NU-1346-011, NU-200411-0379, MILLENNIUM-NU-04H4, LILLY-NU-04H4, VEL-03-082
Study First Received: February 9, 2006
Last Updated: July 7, 2009
ClinicalTrials.gov Identifier: NCT00290706     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 3 follicular lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Lymphoma, T-Cell
Therapeutic Uses
Gemcitabine
Lymphoma
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Bortezomib
Enzyme Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Protease Inhibitors
Lymphatic Diseases
Neoplasms
Radiation-Sensitizing Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on February 08, 2010