Ph2 Gem/Nov/Rituxan Rel/Ref MantleCell

Phase 2

Completed

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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Experimental arm	gemcitabine	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.
Experimental arm	mitoxantrone	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.
Experimental arm	rituximab	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (CR + PR)	2 years	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Response	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.	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.
Overall Survival (OS) Rate at 1 Year	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.
Progression-free Survival Rate at 1 Year.	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.