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

Sponsor:	Northwestern University
Collaborators:	Eli Lilly and Company Millennium Pharmaceuticals, Inc.
Information provided by:	Northwestern University
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:	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 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:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Bortezomib

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

To evaluate the response rate (combined complete remission [CR] and partial remission [PR])of the combination of study drugs in patients with relapsed or refractory B- and T-cell NHL [ Time Frame: At screening and after completing cycle 3, cycle 6 and 30 days after cycle 8 ] [ Designated as safety issue: No ]
Disease evaluations to evaluate the response rate of the combination of study drugs in patients with relapsed or refractory B- and T-cell NHL will be done by CT scan at screening and after completing cycle 3, cycle 6 and 30 days after cycle 8.

Secondary Outcome Measures:

Evaluate 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 ] [ Designated as safety issue: No ]
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
Evaluate overall survival [ Time Frame: Every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years ] [ Designated as safety issue: No ]
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
Evaluate safety and tolerability of bortezomib and gemcitabine therapy [ Time Frame: At screening, on day 1 and on day 15 of each treatment cycle while on active treatment; then every 3 months while in follow-up ] [ Designated as safety issue: Yes ]
Safety and tolerability of the study drugs will be assessed at screening, on day 1 and on day 15 of each treatment cycle while on active treatment; then every 3 months while in follow-up.

Estimated Enrollment:	28
Study Start Date:	September 2005
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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®

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
Northwestern University
Chicago, Illinois, United States, 60611
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637
Veterans Affairs Medical Center - Lakeside Chicago
Chicago, Illinois, United States, 60611

Sponsors and Collaborators

Northwestern University

Eli Lilly and Company

Millennium Pharmaceuticals, Inc.

Investigators

Principal Investigator:

Leo Gordon, MD

Northwestern University

More Information

No publications provided

Responsible Party:	Andrew Evens, DO, Northwestern University
ClinicalTrials.gov Identifier:	NCT00290706 History of Changes
Other Study ID Numbers:	NU 04H4, NU 04H4, VEL-03-082, STU00007425
Study First Received:	February 9, 2006
Last Updated:	May 18, 2011
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

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:

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
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012