Non-Hodgkin's Lymphoma (NHL)
Conditions
Brief summary
The primary objective of the study is to determine the efficacy, as measured by overall response (complete response + partial response) of bendamustine in combination with ofatumumab in previously untreated patients with indolent B-Cell Non-Hodgkin's Lymphoma (NHL).
Interventions
DRUGBendamustine hydrochloride
Bendamustine will be administered at 90 mg/m\^2 as a 30-minute intravenous (iv) infusion on days 1 and 2 of each cycle.
DRUGOfatumumab
Ofatumumab will be administered at 300 mg as an iv infusion on day 1 and 1000 mg on day 8 of cycle 1 and 1000 mg on day 1 of each subsequent cycle.
Sponsors
Cephalon
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
Key Inclusion Criteria: * The patient has histopathologic confirmation of one of the protocol-specific CD20+ B-cell non-Hodgkin's lymphomas. Tissue diagnostic procedures must be performed within 6 months of study entry and with biopsy material available for review. * The patient meets 1 of the following need-for-treatment criteria: 1. Presence of at least 1 of the following B-symptoms: * fever (\>38ºC) of unclear etiology * night sweats * weight loss of greater than 10% within the prior 6 months 2. large tumor mass (bulky disease) characterized by lymphomas with a diameter of more than 3 cm in 3 or more regions or by a lymphoma with a diameter of more than 7 cm in 1 region 3. presence of lymphoma-related complications 4. hyperviscosity syndrome due to monoclonal gammopathy * The patient's tumor is verified to be CD20+ positive from current or previous excisional or incisional tissue diagnostic procedures performed within 6 months of study entry. * The screening phase CT scan (based on local evaluation) shows: * 2 or more clearly demarcated lesions with a largest diameter ≥1.5 cm, or * 1 clearly demarcated lesion with a largest diameter ≥2.0 cm * The patient was not previously treated for indolent lymphoma (with the exception of a single course of local radiation therapy not exceeding 2 adjacent lymph node regions). * The patient has adequate hematologic and hepatic function. * The patient has Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. * The patient has serum creatinine of 2.0 mg/dL or less or creatinine clearance of 30 mL/min or more, based on the Cockcroft-Gault method, or from a 24-hour urine collection. * The patient is willing to comply with contraception requirements. Key
Exclusion criteria
The patient: * Has small lymphocytic lymphoma or mantle cell lymphoma. * Has documented history of central nervous system (CNS) lymphomatous involvement. * Has or has had an active malignancy, other than NHL, within the past 3 years except for localized prostate cancer without evidence of bone metastases, bladder, cervical, or breast carcinoma in-situ, or non-melanoma skin cancer . * Has New York Heart Association (NYHC) Class III or IV heart failure, uncontrolled arrythmias or unstable angina, electrocardiographic evidence of active ischemia or active conduction system abnormalities, or myocardial infarction within the last 6 months. * Has known human immunodeficiency virus (HIV) infection. * Has acute or chronic hepatitis B or hepatitis C infection. * Is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.) * Has any serious uncontrolled, medical or psychological disorder that would impair the ability of the subject to receive study drugs. * Has received another investigational agent within 30 days of study entry. * Has known hypersensitivity to mannitol. * Has Ann Arbor stage I disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR), as Determined by the International Working Group (IWG) Criteria As Assessed by Investigators | up to Week 32 | The IWG criteria (Cheson et al 2007) for a CR is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A PR is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Best Overall Response of Complete Response (CR), as Determined by the International Working Group (IWG) Criteria As Assessed by Investigators | up to Week 32 | The IWG criteria (Cheson et al 2007) for a CR is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. |
Countries
Belgium, Israel, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bendamustine and Ofatumumab There are 6 planned and 2 optional 28-day cycles in which participants are administered both bendamustine and ofatumumab in the following doses: Bendamustine administered at 90 mg/m\^2 intravenously (iv) on study days 1 and 2. Ofatumumab administered at 300 mg iv on day 1 and 1000 mg iv on day 8 of cycle 1. Ofatumumab administered at 1000 mg iv on day 1 of all additional cycles. | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Bendamustine and Ofatumumab |
|---|---|
| Age Continuous | 59.1 years STANDARD_DEVIATION 10.77 |
| Age, Customized <65 years | 31 participants |
| Age, Customized >=65 years | 18 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants |
| Race/Ethnicity, Customized Asian | 2 participants |
| Race/Ethnicity, Customized Black | 2 participants |
| Race/Ethnicity, Customized Other | 0 participants |
| Race/Ethnicity, Customized Pacific Islander | 0 participants |
| Race/Ethnicity, Customized White | 44 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 49 / 49 |
| serious Total, serious adverse events | 14 / 49 |
Outcome results
Primary
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR), as Determined by the International Working Group (IWG) Criteria As Assessed by Investigators
The IWG criteria (Cheson et al 2007) for a CR is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A PR is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed.
Time frame: up to Week 32
Population: Safety population of participants who were treated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bendamustine and Ofatumumab | Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR), as Determined by the International Working Group (IWG) Criteria As Assessed by Investigators | 90 percentage of participants |
Secondary
Percentage of Participants With a Best Overall Response of Complete Response (CR), as Determined by the International Working Group (IWG) Criteria As Assessed by Investigators
The IWG criteria (Cheson et al 2007) for a CR is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
Time frame: up to Week 32
Population: Safety population of participants who were treated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bendamustine and Ofatumumab | Percentage of Participants With a Best Overall Response of Complete Response (CR), as Determined by the International Working Group (IWG) Criteria As Assessed by Investigators | 67 percentage of participants |