Clinical trial NCT00290706: A Phase I/II Trial of VELCADE & Gemcitabine for Patients With Relapsed or Refractory Aggressive B- and T-cell Non-Hodgkin's Lymphoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Keywords: 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
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
name: Millennium Pharmaceuticals, Inc.
First posted: 2006-02-13
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Response Rate in Patients With Relapsed or Refractory B- and T-cell NHL With Gemcitabine and Bortezomib Combination Treatment.
timeFrame: At screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8
Secondary outcomes:
measure: Time to Treatment Failure and Duration of Response
timeFrame: At screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years
measure: Overall Survival
timeFrame: Every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years
measure: Evaluate Safety and Tolerability of Bortezomib and Gemcitabine Therapy
timeFrame: During treatment through a maximum of 8 Cycles (1 Cycle = 28 Days) and 30 days post last treatment
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
Study officials:
affiliation: Northwestern University
name: Leo Gordon, MD
role: PRINCIPAL_INVESTIGATOR
References: