Non-Hodgkin's Lymphoma
Conditions
Keywords
Bortezomib, Bendamustine, Rituximab, Relapsed, Refractory, Mantle Cell, Indolent
Brief summary
The purpose of this study is to evaluate how non-Hodgkin's lymphoma that has not responded to, or that has returned after standard treatment, responds to bortezomib, rituximab and bendamustine, and also to see what effects this drug combination have on this cancer.
Interventions
DRUGbortezomib
1.3 mg/m\^2 on days 1, 4, 8, 11
DRUGbendamustine
90 mg/m\^2 days 1 and 4
DRUGrituximab
375 mg/m\^2 day 1
Sponsors
Millennium Pharmaceuticals, Inc.
Cephalon
University of Rochester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Voluntary written informed consent before performance of any study-specific procedure not part of routine medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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 acceptable method of birth control for duration of study. * Male subject agrees to use acceptable method for contraception for duration of study. * Histologically-confirmed indolent or mantle cell lymphoma, utilizing the World Health Organization (WHO) classification. The biopsy must fulfill one of the following criteria: * Follicular lymphoma, grades 1-3 * Marginal zone lymphoma * Small lymphocytic lymphoma (circulating lymphocyte count must be \< 5,000) * Lymphoplasmacytic lymphoma * Mantle cell lymphoma \[confirmed by cyclin D1+ or FISH for t(11;14)\] * Age ≥ 18 years * Must have received at least one prior chemotherapy regimen for lymphoma. Patients treated only with antibody therapy or only with radiation therapy are not eligible. * Zubrod performance status ≤ 3 * Patients must have measurable disease or an indication to receive additional therapy
Exclusion criteria
* Patient has platelet count of ≤75,000/mm\^3 within 14 days before enrollment. * Patient has absolute neutrophil count of \< 1,000/mm\^3 within 14 days before enrollment. * Patient has calculated or measured creatinine clearance of \<30 mL/minute within 14 days before enrollment. * Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment. * Myocardial infarction within 6 months prior to enrollment or has New York Heart Association 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 ECG abnormality at Screening has to be documented by the investigator as not medically relevant. * Patient has hypersensitivity to boron or mannitol * Female subject is pregnant or breast-feeding. Confirmation subject is not pregnant must be established by negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. * Patient has received chemotherapy or antibody therapy within 28 days before enrollment * Serious medical or psychiatric illness likely to interfere with participation in this clinical study. * Patient has received other investigational drugs with 14 days before enrollment * 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. * Prior exposure to bendamustine * Prior exposure to bortezomib if Time to Progression (TTP) after bortezomib containing regimen was \< 6 months. If TTP after bortezomib containing regimen was \> 6 months, then patient is allowed to enroll on the study. * Patient has concomitant active malignancy requiring therapy * Patient is known to be HIV positive (test result not required for enrollment). * History of solid organ transplantation, or post transplant lymphoproliferative disorder * Patient has history of allogeneic stem cell transplantation. * Patient has history of autologous stem cell transplantation or radioimmunotherapy within the previous 4 months. * Patient has received any other investigational drugs within 14 days prior to enrollment * History of, or clinically apparent CNS lymphoma * Any clinically significant abnormality in screening blood chemistry, hematology, or urinalysis results that, in the judgment of the investigator, would impede adequate evaluation of adverse events and/or response to treatment, or that requires aggressive intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression Free Survival at 2 Years | Two years | To determine the progression-free survival following treatment with the BVR combination in patients with relapsed or refractory indolent and mantle cell non-Hodgkin lymphoma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity of Drug Combination in the Subjects | Two years | — |
| Overall Response Rate (ORR) | Two years | Overall response rate (ORR)to protocol treatment - Partial response, Complete response, etc. |
Countries
United States
Participant flow
Recruitment details
Recruitment at the University of Rochester Medical Center, Weill Cornell Medical Center and the University of Nebraska began in October 2007 and ended in March 2009. Patients were recruited in a medial clinic setting.
Participants by arm
| Arm | Count |
|---|---|
| Lymphoma Subjects Subjects that met all eligibility criteria and were given study treatment. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Disease Progression | 4 |
Baseline characteristics
| Characteristic | Lymphoma Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 64.8 years STANDARD_DEVIATION 20 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 13 / 30 |
Outcome results
Primary
Number of Participants With Progression Free Survival at 2 Years
To determine the progression-free survival following treatment with the BVR combination in patients with relapsed or refractory indolent and mantle cell non-Hodgkin lymphoma.
Time frame: Two years
Population: Analysis was per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lymphoma Subjects | Number of Participants With Progression Free Survival at 2 Years | 13 Participants |
Secondary
Overall Response Rate (ORR)
Overall response rate (ORR)to protocol treatment - Partial response, Complete response, etc.
Time frame: Two years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lymphoma Subjects | Overall Response Rate (ORR) | 13 Lymphoma Subjects |
Secondary
Toxicity of Drug Combination in the Subjects
Time frame: Two years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lymphoma Subjects | Toxicity of Drug Combination in the Subjects | 13 Lymphoma Subjects |