Ph2 Gem/Nov/Rituxan Rel/Ref MantleCell

Study Overview
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Brief Summary
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To determine the efficacy (response rate) produced by the combination of Gemzar, Novantrone, and Rituxan in relapsed or refractory MCL

Official Title
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A Phase II Study of Gemzar, Novantrone and Rituxan in Relapsed or Refractory Mantle Cell Lymphoma (MCL) (B9E-US-X436)

Conditions
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Relapsed or Refractory Mantle Cell Lymphoma (MCL)

Intervention / Treatment
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* Drug: gemcitabine
* Drug: mitoxantrone
* Drug: rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage III or IV, histologically confirmed relapsed or refractory MCL as reviewed by the SI Is CD20 positive (by immunohistochemistry or FACS) Is Cyclin D positive (by immunohistochemistry or FACS) Has received prior chemotherapy (required minimum of 1 prior therapies) Has received prior treatment with Rituxan Has an ECOG Performance Status (PS) 0-2 Is greater than or equal to 18 years of age Has appropriate laboratory values (please refer to protocol for specific laboratory values) If a history of cardiac disease is indicated, patient has an LVEF greater than or equal to 50% (MUGA) Has a negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential) If fertile, patient (male or female) has agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a period of 2 months thereafter Has signed a Patient Informed Consent Form Has signed a Patient Authorization Form Exclusion Criteria: Has other lymphomas not classified as MCL Has had prior treatment with Gemzar and/or Novantrone A history of known hypersensitivity to Gemzar, Novantrone, Rituxan, or any component of these drugs Has a history of hypersensitivity to murine-cell derived therapeutics Has a LVEF indicative of a cardiac condition (LVEF < 50%) Is receiving concurrent immunotherapy Has evidence of CNS involvement Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma insitu of uterine cervix), which could affect the diagnosis or assessment of any of the study drugs Is a pregnant or nursing woman Is unable to comply with requirements of study

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental arm<br>Patients will be treated a maximum of 8 cycles or until the patient has evidence of a response, progressive disease, or until intolerable toxicity develops. Patients with a complete response will receive an additional 2 cycles of treatment (not to exceed 8 cycles). Drug order is gemcitabine, mitoxantrone, and rituximab. | Drug: gemcitabine<br>* 900 mg/m2 on Days 1 and 8 of each 21-day cycle The order of administration will be: Gemzar-->Novantrone-->Rituxan.<br>* Other names: Gemzar;Drug: mitoxantrone<br>* Novantrone 10 mg/m2on Day 1. The order of administration will be: Gemzar-->Novantrone-->Rituxan.<br>* Other names: Novantrone;Drug: rituximab<br>* Rituxan 375 mg/m2 on Day 1. The order of administration will be: Gemzar-->Novantrone-->Rituxan.<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (CR + PR) | Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. | From date of randomization until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 33 months. | 
| Overall Survival (OS) Rate at 1 Year | OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. | 1 year. | 
| Progression-free Survival Rate at 1 Year. | PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. | 1 year. |