Combination Chemotherapy With or Without Bortezomib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with bortezomib may kill more cancer cells. It is not yet known whether combination chemotherapy is more effective with or without bortezomib in treating mantle cell lymphoma. PURPOSE: This randomized phase II trial is studying combination chemotherapy and bortezomib to see how well they work compared with combination chemotherapy alone in treating patients with relapsed or refractory mantle cell lymphoma. Combination chemotherapy alone (Arm I) has been discontinued April 2012 on recommendation of the DMC.

Detailed Description
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OBJECTIVES: Primary To evaluate the rates of overall response (complete response [CR], CR unconfirmed [CRu], and partial response). Secondary To evaluate the rates of CR and CRu. To determine the median time to progression. To determine the median overall survival. To evaluate the toxicity and tolerability. To compare the responses to these treatment regimens with those from first line therapy. To compare the quality of life. OUTLINE: This is a randomized, open-label, parallel group, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I (CHOP): Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Arm I has been discontinued April 2012 on recommendation of the DMC. Arm II (CHOP with bortezomib): Patients receive bortezomib IV over 3-5 seconds on days 1 and 8; doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1; and oral prednisolone on days 1-5. In both arms, treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients complete quality of life questionnaires at baseline, prior to each treatment course, and then at 30 days after completion of treatment. After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter.

Official Title
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A Parallel Randomised Phase II Trial of CHOP Chemotherapy With or Without Bortezomib in Relapsed Mantle Cell Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: bortezomib
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: prednisolone
* Drug: vincristine sulfate
* Other: questionnaire administration
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of mantle cell lymphoma (MCL) Expression of cyclin D1 or evidence of t(11;14) translocation by cytogenetics, FISH, or polymerase chain reaction Refractory to or relapsed or progressed after first line antineoplastic therapy Measurable disease PATIENT CHARACTERISTICS: Inclusion criteria: Karnofsky performance status (PS) 50-100% OR ECOG PS 0-2 ANC ≥ 1,000/mm³ (not related to lymphoma) Platelet count ≥ 30,000/mm³ AST and ALT ≤ 3 times upper limit of normal (ULN) Total bilirubin ≤ 2 times ULN Creatinine clearance ≥ 20 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Exclusion criteria: Known serological positivity for HBV, HCV, or HIV History of allergic reaction attributable to compounds containing boron or mannitol Diagnosed or treated for a malignancy other than MCL within the past 5 years except for completely resected basal cell or squamous cell carcinoma of the skin or any in situ malignancy Active systemic infection requiring treatment Serious medical or psychiatric illness that would preclude study participation PRIOR CONCURRENT THERAPY: Inclusion criteria: Toxic effects of prior therapy or surgery must be resolved to ≤ grade 2 Prior splenectomy or localized radiotherapy allowed Any prior chemotherapy regimen allowed Chemotherapy may have been given in combination with rituximab Concurrent enrollment in a nontreatment study allowed, provided it does not interfere with participation in this study Exclusion criteria: Prior bortezomib Antineoplastic therapy within the past 3 weeks Nitrosoureas within the past 6 weeks Rituximab, alemtuzumab (Campath®), or other unconjugated therapeutic antibody within the past 4 weeks Radiotherapy within the past 3 weeks Major surgery within the past 2 weeks Concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bortezomib plus CHOP<br>Patients receive bortezomib IV over 3-5 seconds on days 1 and 8; doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1; and oral prednisolone on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients complete quality of life questionnaires at baseline, prior to each treatment course, and then at 30 days after completion of treatment. After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter. | Drug: bortezomib<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: prednisolone<br> <br> Drug: vincristine sulfate<br> <br> Other: questionnaire administration<br> <br> Procedure: quality-of-life assessment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease progression | The follow-up visits will be at 30 days after last dose of study drug and after that every 12 weeks until: Progressive disease, initiation of further anti-neoplastic therapy, patient decision to withdraw from the study, patient death. | 30 days and every 12 weeks | 
| Unacceptable toxicity or tolerability as assessed by NCI CTCAE v3.0 | The follow-up visits will be at 30 days after last dose of study drug and after that every 12 weeks until: Progressive disease, initiation of further anti-neoplastic therapy, patient decision to withdraw from the study, patient death. | continual after first drug dose | 

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