Bortezomib and Gemcitabine in Treating Patients With Relapsed Mantle Cell Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. 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 help gemcitabine work better by making cancer cells more sensitive to the drug. PURPOSE: This phase II trial is studying how well giving bortezomib together with gemcitabine works in treating patients with relapsed mantle cell lymphoma.

Detailed Description
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OBJECTIVES: Determine the efficacy (response rate) of bortezomib and gemcitabine hydrochloride in patients with relapsed mantle cell lymphoma. Determine the toxicity of this regimen in these patients. Determine the time to progression and duration of response in patients treated with this regimen. OUTLINE: This is a nonrandomized, multicenter study. Patients receive bortezomib IV on days 1, 4, 8, and 11 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter until relapse/progression.

Official Title
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A Phase II Study of Bortezomib and Gemcitabine in Patients With Relapsed Mantle Cell Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: bortezomib
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed mantle cell lymphoma Relapsed disease Not refractory to prior therapy Must have received 1-3 prior systemic chemotherapy regimens AND has had no disease progression while receiving chemotherapy or within 1 month of last dose of most recent therapy Clinically and/or radiologically documented disease At least 1 site of disease must be bidimensionally measurable by CT scan or MRI with ≥ 1 lesion meeting 1 of the following criteria: Lymph nodes ≥ 1.5 cm x 1.5 cm by spiral CT scan Non-nodal lesion ≥ 1 cm x 1 cm by MRI, CT scan, or physical exam No nonmeasurable disease only No preexisting ascites or pleural effusion ≥ grade 2 No known CNS involvement by lymphoma PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 12 weeks Absolute granulocyte count ≥ 1,500/mm³ Platelet count ≥ 75,000/mm³ Creatinine ≤ 1.5 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN AST or ALT ≤ 2.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception LVEF ≥ 45% by echocardiogram or MUGA No history of allergic reactions attributed to compounds containing boron or mannitol No preexisting edema ≥ grade 2 No preexisting neuropathy (sensory and/or pain) ≥ grade 2 No preexisting shortness of breath ≥ grade 2 No history of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years No other serious illness or medical condition that would preclude compliance with study requirements, including any of the following: Serious uncontrolled infection Uncontrolled or severe cardiovascular disease, including any of the following: Myocardial infarction within the past 6 months New York Heart Association class III-IV heart failure Uncontrolled angina Clinically significant pericardial disease Cardiac amyloidosis Significant neurological disorder PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 6 weeks since prior chemotherapy No prior radioactive monoclonal antibody therapy No prior bortezomib No prior investigational therapy (except for flavopiridol) No prior radiotherapy to > 25% of functioning bone marrow At least 4 weeks since prior radiotherapy and recovered Low-dose, nonmyelosuppressive radiotherapy may be allowed At least 2 weeks since prior major surgery No other concurrent anticancer therapy No concurrent corticosteroids No other concurrent cytotoxic chemotherapy No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bortezomib + Gemcitabine<br> | Drug: bortezomib<br>* 1.0 mg/m2 IV; injection bolus (3-5 sec) Twice weekly x 2 weeks every three weeks<br>Drug: gemcitabine hydrochloride<br>* 1000 mg/m2 IV; injection 30 minute infusion Once weekly x 2 weeks every three weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response (overall response rate with 95% confidence interval) |  | each cycle | 
| Time to progression at median time |  | each cycle and every 3 months after treatment | 
| Duration of response (median and range) |  | each cycle and every 3 months after treatment | 
| Rate of stable disease and progressive disease |  | each cycle and every 3 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent mantle cell lymphoma