Relapsed or Refractory Mantle Cell Lymphoma (MCL)
Conditions
Brief summary
To determine the efficacy (response rate) produced by the combination of Gemzar, Novantrone, and Rituxan in relapsed or refractory MCL
Interventions
DRUGgemcitabine
900 mg/m2 on Days 1 and 8 of each 21-day cycle The order of administration will be: Gemzar--\>Novantrone--\>Rituxan.
DRUGmitoxantrone
Novantrone 10 mg/m2on Day 1. The order of administration will be: Gemzar--\>Novantrone--\>Rituxan.
DRUGrituximab
Rituxan 375 mg/m2 on Day 1. The order of administration will be: Gemzar--\>Novantrone--\>Rituxan.
Sponsors
Eli Lilly and Company
US Oncology Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemzar + Novantrone + Rituxan Gemzar, Novantrone, and Rituxan in relapsed or refractory mantle cell lymphoma (MCL) | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Investigator Request | 1 |
| Overall Study | Patient Request | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Gemzar + Novantrone + Rituxan |
|---|---|
| Age, Continuous | 68 years STANDARD_DEVIATION 12.3 |
| Race/Ethnicity, Customized Caucasian | 16 participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 4 / 15 |
Outcome results
Primary
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.
Time frame: 2 years
Population: Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemzar + Novantrone + Rituxan | Objective Response Rate (CR + PR) | 46.7 percentage of participants |
Secondary
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.
Time frame: 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.
Population: For patients who achieve a major objective response (CR or PR) the time to response will be assessed as the date of registration to the date of response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemzar + Novantrone + Rituxan | Duration of Response | 7.9 months |
Secondary
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.
Time frame: 1 year.
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemzar + Novantrone + Rituxan | Overall Survival (OS) Rate at 1 Year | 0.57 Probability of Survival |
Secondary
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.
Time frame: 1 year.
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemzar + Novantrone + Rituxan | Progression-free Survival Rate at 1 Year. | 0.54 Probability of Progression-free Survival |