Lymphoma, Large-Cell, Diffuse, Lymphoma, B-Cell
Conditions
Keywords
diffuse large B-cell lymphoma, Bortezomib, CHOP, Lenograstim
Brief summary
Diffuse large B-cell lymphoma is a most prevalent non-Hodgkin's lymphoma. Recently the clinical results have been improved with new drugs and new modalities such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks. Bortezomib is well known to be effective for multiple myeloma and has been being tried for other malignancies including lymphoma. The investigators will incorporate Bortezomib to CHOP every 2 weeks to further improve the clinical efficacy in diffuse large B-cell lymphoma.
Detailed description
Intended number of patients: 63 patients in total * Phase I: 9 patients for 3 levels * Phase II: 50 patients plus 3 patient from Phase I at MTD level * Plus 4 patients: considering 5% follow-up loss rate Study design and methodology: For phase I, 9 patients; 3 levels of bortezomib (1.0, 1.3 and 1.6 mg/m2), 3 patients at each dose level. If escalation of bortezomib beyond 1.0 mg/m2 is not possible, the trial will be stopped. For phase II, 53 patients (3 from phase I at MTD level); Reject when complete response rate equal or less than 12/19 or 37/53 by Simon two-stage optimal phase II design. Treatments: * Bortezomib: For phase I, 3 dose levels (1.0, 1.3 or 1.6 mg/m2), days 1 and 4, every 2 weeks. For phase II, suggested dose of Bortezomib through phase I, days 1 and 4, every 2 weeks. * CHOP2: cyclophosphamide 750mg/ m2 day 1, vincristine 1.4 mg/ m2 (max. 2 mg) day 1, doxorubicin 50 mg/ m2 day 1, prednisolone 100 mg days 1-5, every 2 weeks. * G-CSF: Lenograstim 5 microgram/kg subcutaneously days 4-13 every 2 weeks.
Interventions
DRUGBortezomib
Bortezomib: For phase I, 3 dose levels (1.0, 1.3 or 1.6 mg/m2), days 1 and 4, every 2 weeks. For phase II, suggested dose of Bortezomib through phase I, days 1 and 4, every 2 weeks.
DRUGCyclophosphamide
cyclophosphamide 750mg/m2 day 1, every 2 weeks
DRUGDoxorubicin
doxorubicin 50 mg/m2 day 1, every 2 weeks
DRUGVincristine
vincristine 1.4 mg/m2 (max. 2 mg) day 1, every 2 weeks
DRUGPrednisolone
prednisolone 100 mg days 1-5, every 2 weeks
DRUGLenograstim
Lenograstim 5 microgram/kg subcutaneously days 4-13 every 2 weeks
Sponsors
Janssen Korea, Ltd., Korea
Asan Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed DLBCL * Age 70 years or less * Previously untreated * Performance status: ECOG 0-2 * Advanced stage: stage III, IV, or non-contiguous stage II * Measurable disease: 1 cm or more by spiral CT * Normal liver function
Exclusion criteria
* Platelet count less than 75,000/microL within 14 days before enrollment. * Absolute neutrophil count of less than 1,500/microlL within 14 days before enrollment. * Cr more than 2.0 mg/dL and/or calculated or measured creatinine clearance less than 50 mL/min within 14 days before enrollment. * Peripheral neuropathy of Grade 2 or worse within 14 days before enrollment. * Hypersensitivity to bortezomib, boron or mannitol. * Female subject is pregnant or breast-feeding. * Other investigational drugs with 14 days before enrollment * Serious medical or psychiatric illness likely to interfere with participation in this clinical study. * Uncontrolled or severe cardiovascular disease, including MI within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Achieved Complete Response | 14 weeks | All patients,9 patients of phase I study and 40 patietns in phase II stuay, were assessed with International Working Group response criteria assessed by CT; Complete Response (CR), Disappearance of all detectable clinical and radiographic evidence of disease and diappearance of all disease-related symptoms. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Patients Who Experienced Adverse Events | 6 months |
Countries
South Korea
Participant flow
Recruitment details
Duration of patient enrollment: From 15-Dec-2006 to 02-May-2009
Participants by arm
| Arm | Count |
|---|---|
| Bortezomib + CHOP Every 2 Weeks CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone | 49 |
| Total | 49 |
Baseline characteristics
| Characteristic | Bortezomib + CHOP Every 2 Weeks |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants |
| Age Continuous | 52 years STANDARD_DEVIATION 10 |
| Region of Enrollment Korea, Republic of | 49 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 27 / 49 |
| serious Total, serious adverse events | 22 / 49 |
Outcome results
Primary
Number of Patients Who Achieved Complete Response
All patients,9 patients of phase I study and 40 patietns in phase II stuay, were assessed with International Working Group response criteria assessed by CT; Complete Response (CR), Disappearance of all detectable clinical and radiographic evidence of disease and diappearance of all disease-related symptoms.
Time frame: 14 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bortezomib + CHOP Every 2 Weeks | Number of Patients Who Achieved Complete Response | 32 participants |
Secondary
Number of Patients Who Experienced Adverse Events
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bortezomib + CHOP Every 2 Weeks | Number of Patients Who Experienced Adverse Events | 49 participants |