Contiguous Stage II Mantle Cell Lymphoma, Noncontiguous Stage II Mantle Cell Lymphoma, Recurrent Mantle Cell Lymphoma, Stage III Mantle Cell Lymphoma, Stage I Mantle Cell Lymphoma, Stage IV Mantle Cell Lymphoma
Conditions
Brief summary
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bortezomib and rituximab together works in treating patients with mantle cell lymphoma who have previously undergone stem cell transplantation
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the two year disease free survival in mantle cell lymphoma (MCL) patients treated with bortezomib + rituximab after hematopoietic stem cell transplantation (HSCT). SECONDARY OBJECTIVES: I. To evaluate the toxicity profile, safety, overall survival, time to treatment failure, remission duration, and biological markers of mantle cell lymphoma patients treated with bortezomib + rituximab after autologous hematopoietic stem cell transplantation. OUTLINE: Patients receive bortezomib subcutaneously (SC) or intravenously (IV) over 3-5 seconds and rituximab IV on days 1, 8, 15, and 22. Treatment with bortezomib repeats every 3 months for up to 8 courses and treatment with rituximab repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 3 years.
Interventions
DRUGbortezomib
Given SC or IV
BIOLOGICALrituximab
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
OTHERimmunohistochemistry staining method
Correlative studies
GENETICRNA analysis
Correlative studies
GENETICgene expression analysis
Correlative studies
GENETICDNA analysis
Correlative studies
OTHERpharmacological study
Correlative studies
OTHERpharmacogenomic studies
Correlative studies
OTHERQuestionnaire Administration
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histological documented or cytological confirmed mantle cell lymphoma; cyclin D1 must be present as evidenced by either fluorescence in situ hybridization (FISH) or immunohistochemical staining * Patients must have undergone autologous hematopoietic stem cell transplantation (AHCT) and achieved engraftment by day (D)60-180 as evidenced by absolute neutrophil count (ANC) \> 1000/mcL and platelets (Plt) \> 75,000/mcL * Patients must be in complete remission at D60-180 after AHCT as evidenced by computed tomography (CT) scan of the neck/chest/abdomen (abd)/pelvis or CT/positron emission tomography (PET) scans * Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care * Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study * Male subject agrees to use an acceptable method for contraception for the duration of the study * Life expectancy of greater than 3 months * Karnofsky \> 60% * ANC \> 1000/mcL * Plts \> 75,000/mcL * Total bilirubin within normal institutional limits, patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 2.5 x institutional upper limit of normal * Creatinine up to and including 2 mg/dL
Exclusion criteria
* Patient has \>= grade 2 peripheral neuropathy within 14 days before enrollment and at D60-180 after AHCT; patients who had \>= grade 2 peripheral neuropathy within 14 days before enrollment but resolves to grade 1 or lower peripheral neuropathy at D60-D180 after AHCT can be enrolled at this time * Patient has \> 1.5 x upper limit of normal (ULN) total bilirubin unless history of Gilbert's syndrome * Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiographic (ECG) abnormality at screening has to be documented by the investigator as not medically relevant * Patient has hypersensitivity to bortezomib, boron or mannitol * Female subject is pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women * Patient has received other investigational drugs with 14 days before treatment of treatment with bortezomib + rituximab * Serious medical or psychiatric illness likely to interfere with participation in this clinical study * Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy * Patients with other active malignancies (no evidence of other cancer or life expectancy greater than 5 years) are ineligible for this study * Human immunodeficiency virus (HIV) positive patients or hepatitis B or C positive patients * Patients with active central nervous system (CNS) disease or history of brain metastases (mets) are excluded from study * Prior exposure to either bortezomib or rituximab is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Two-year Disease-free Survival | Participants were followed up to 5 years after initial treatment and Kaplan-Meier survival analysis was used to generate the two-year disease-free survival estimate presented. | Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Two-year Overall Survival | Participants were followed up to 5 years after initial treatment and Kaplan-Meier survival analysis was used to generate the two-year overall survival estimate presented. | Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula. |
| Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment | Participants were followed up to 5 years after initial treatment. | Observed toxicities will be summarized in terms of type, severity (graded by NCI CTCAE version 4.0) and attribution. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Bortezomib and Rituximab) Doses of bortezomib given is 1.3 mg/m2 weekly x 4 weeks given every 3 month x 8 cycles. Doses of RITUXAN given is 375 mg/m2 give weekly x 4 weeks given every 6 month for 4 cycles.
bortezomib: Given SC or IV
rituximab: Given IV
laboratory biomarker analysis: Correlative studies
immunohistochemistry staining method: Correlative studies
RNA analysis: Correlative studies
gene expression analysis: Correlative studies
DNA analysis: Correlative studies
pharmacological study: Correlative studies
pharmacogenomic studies: Correlative studies
Questionnaire Administration | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | Treatment (Bortezomib and Rituximab) |
|---|---|
| Age, Continuous | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 23 |
| other Total, other adverse events | 23 / 23 |
| serious Total, serious adverse events | 7 / 23 |
Outcome results
Primary
Two-year Disease-free Survival
Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula.
Time frame: Participants were followed up to 5 years after initial treatment and Kaplan-Meier survival analysis was used to generate the two-year disease-free survival estimate presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Bortezomib and Rituximab) | Two-year Disease-free Survival | 90 percentage of participants |
Secondary
Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment
Observed toxicities will be summarized in terms of type, severity (graded by NCI CTCAE version 4.0) and attribution.
Time frame: Participants were followed up to 5 years after initial treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Bortezomib and Rituximab) | Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment | Neutropenia | 17 Participants |
| Treatment (Bortezomib and Rituximab) | Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment | Lymphopenia | 8 Participants |
| Treatment (Bortezomib and Rituximab) | Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment | Pneumonia | 2 Participants |
| Treatment (Bortezomib and Rituximab) | Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment | Anemia | 2 Participants |
| Treatment (Bortezomib and Rituximab) | Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment | Lung infection | 2 Participants |
| Treatment (Bortezomib and Rituximab) | Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment | Skin infection | 1 Participants |
| Treatment (Bortezomib and Rituximab) | Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment | Wound infection | 1 Participants |
| Treatment (Bortezomib and Rituximab) | Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment | Hypertension | 1 Participants |
| Treatment (Bortezomib and Rituximab) | Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment | Thrombocytopenia | 1 Participants |
Secondary
Two-year Overall Survival
Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula.
Time frame: Participants were followed up to 5 years after initial treatment and Kaplan-Meier survival analysis was used to generate the two-year overall survival estimate presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Bortezomib and Rituximab) | Two-year Overall Survival | 95 percentage of participants |