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A Phase I/II Trial of VELCADE & Gemcitabine for Patients With Relapsed or Refractory Aggressive B- and T-cell Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00290706
Recruitment Status : Terminated (Closed per Data Monitoring Committee due to lack of efficacy)
First Posted : February 13, 2006
Results First Posted : May 28, 2019
Last Update Posted : May 28, 2019
Sponsor:
Collaborators:
Eli Lilly and Company
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Northwestern University

Brief Summary:

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 or disease Intervention/treatment Phase
Lymphoma Drug: bortezomib Drug: gemcitabine hydrochloride Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 7, 2006
Actual Primary Completion Date : February 11, 2011
Actual Study Completion Date : September 5, 2012


Arm Intervention/treatment
Experimental: Gemcitabine 800 mg/m2 + Bortezomib IVP over 3-5 seconds
Gemcitabine dose of 800 mg/m2 over 30 minutes followed by Bortezomib IVP given over 3-5 seconds on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.
Drug: bortezomib
Bortezomib 1.6mg/m2 on days 1 and 15 of each cycle, given over 3-5 seconds on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.
Other Names:
  • Velcade®
  • PS-341

Drug: gemcitabine hydrochloride
Gemcitabine dose of 800 mg/m2 over 30 minutes on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.
Other Name: Gemzar®




Primary Outcome Measures :
  1. Response Rate in Patients With Relapsed or Refractory B- and T-cell NHL With Gemcitabine and Bortezomib Combination Treatment. [ Time Frame: At screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8 ]

    Response rate in patients with relapsed or refractory B- and T-cell NHL with Gemcitabine and Bortezomib combination treatment will be defined as the number of patients with Complete Remission [CR] and Partial Remission [PR]. CT scans at screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8 assessed by the Response Criteria for Non-hodgkins Lymphoma will be used to determine response where:

    CR=Complete disappearance of all detectable clinical and radiographic evidence of disease PR=> 50% decrease in SPD of the six largest dominant nodes or nodal masses



Secondary Outcome Measures :
  1. Time to Treatment Failure and Duration of Response [ Time Frame: At screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years ]
    Time to treatment failure and duration of response will be measured by CT Scan at screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years

  2. Overall Survival [ Time Frame: Every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years ]
    Overall survival will be evaluated every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years

  3. Evaluate Safety and Tolerability of Bortezomib and Gemcitabine Therapy [ Time Frame: During treatment through a maximum of 8 Cycles (1 Cycle = 28 Days) and 30 days post last treatment ]

    Safety and tolerability of the study drugs will be assessed on Day 1 and on either Day 8 or Day 15 of each treatment cycle (1 Cycle - 28 days) while on active treatment; and 30 days post last treatment. Adverse Events that are experienced by patients, determined to be either grade 3 or grade 4 and at least possibly related to at least one of the study drugs as assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) will be collected. In general adverse events (AEs) will be graded according to the following:

    Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00290706


Locations
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United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Veterans Affairs Medical Center - Lakeside Chicago
Chicago, Illinois, United States, 60611
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
Northwestern University
Eli Lilly and Company
Millennium Pharmaceuticals, Inc.
Investigators
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Principal Investigator: Leo Gordon, MD Northwestern University
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Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00290706    
Other Study ID Numbers: NU 04H4
NU 04H4 ( Other Identifier: Northwestern University )
VEL-03-082
STU00007425 ( Other Identifier: Northwestern University IRB )
First Posted: February 13, 2006    Key Record Dates
Results First Posted: May 28, 2019
Last Update Posted: May 28, 2019
Last Verified: May 2019
Keywords provided by Northwestern University:
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:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Bortezomib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs