Follicular Lymphoma, Marginal Zone Lymphoma, Small Lymphocytic Lymphoma
Conditions
Keywords
NHL, ofatumumab
Brief summary
Ofatumumab is a drug that works by attaching to the CD20 molecule found on the surface of cancerous B cells, and then triggering the death of those cells. It is approved by the FDA for treatment of another B-cell cancer, chronic lymphocytic leukemia, and also has evidence of success in people who's B-cell lymphomas have relapsed after initial treatments. In this research study we are looking to see if ofatumumab is effective and safe in treating previously untreated B-cell NHL.
Detailed description
* Participants will receive ofatumumab once a week for 8 weeks by intravenous infusion (Days 1, 8, 15, 22, 29, 36, 43, and 50). * Participants will be seen weekly during the 8 week treatment period and will have the following tests and procedures performed: Blood tests, performance status and physical examination.
Interventions
DRUGofatumumab
Weekly infusion for 8 weeks
Sponsors
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
GlaxoSmithKline
Massachusetts General Hospital
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
* Histologically confirmed indolent CD20+B-cell NHL of the following histologies: follicular lymphoma, grades 1-2; Marginal zone lymphoma (extranodal, nodal or splenic); small lymphocytic lymphoma; low-grade B-cell lymphoma not otherwise specified with CD20+ expression * Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 20mm or greater CT scan or MRI * No previous chemotherapy, antibody therapy or radioimmunotherapy for this disease. Patients previously treated with external beam radiation alone are eligible * 18 years of age or older * Life expectancy of greater than 3 months * ECOG Performance status of 0, 1 or 2 * Organ function as described in the protocol * Women of child-bearing potential and men must agree so use adequate contraception prior to study entry and for the duration of study participation
Exclusion criteria
* Prior chemotherapy, antibody therapy or radioimmunotherapy for lymphoma * Participants may not be receiving any other investigational agent * Participants with known brain metastases * History of allergic reactions attributed to compounds of similar chemical or biologic composition to ofatumumab * Prior exposure to ofatumumab or other targeted anti-CD20 therapies including rituximab * Known HIV positivity * Positive serology for Hepatitis B * Positive serology for Hepatitis C * Participants who are candidates for curative radiotherapy, unless radiation therapy is considered too toxic (as in abdominal disease), or is refused by the patient * New York Heart Association Classification III of IV heart disease * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection that is not optimally treated with antibiotics, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant or breastfeeding women * History of a different malignancy are ineligible except for the following circumstances: Individuals with a history of other malignancy are eligible if they have been disease-free for at least one year and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible even if diagnosed and treated within the past 1 year: localized prostate cancer, prostate cancer with elevated PSA but no measurable disease on CT scans or bone scan, cervical cancer in situ, breast ductal carcinoma in situ and non-melanoma skin cancers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Complete Response Rate (CRR) | 1-month post-treatment | Evaluate clinical efficacy of ofatumumab in previously untreated indolent B-cell lymphomas, as measured by complete response rate (CRR). Complete response = all previously enlarged fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET)-positive lymph nodes regressed to normal size (\<=1.5 cm in greatest diameter) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 1-month post-treatment | Evaluate clinical efficacy of ofatumumab in previously untreated indolent B-cell lymphomas, as measured by overall response rate (ORR). Overall response = Complete response (CR) + Partial response (PR) CR = all previously enlarged fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET)-positive lymph nodes regressed to normal size (\<=1.5cm in greatest diameter) PR = \>=50% decrease in SPD of up to six largest dominant masses, no increase in size of other nodes; FDG avid or PET positive before therapy, one or more nodes PET positive at previously involved site, or variably FDG avid or PET negative with regression at CT |
| Progression-free Survival (PFS) | 12 months | Percentage of patients with progression-free survival during 12 months post-treatment progression-free survival: patients live with the disease, but it does not get worse |
| Toxicity: Infusion Reactions, Grade 3-4 Infections, and Neutropenia | 2 years | Evaluate safety of ofatumumab monotherapy in this patient population Toxicities are graded 1 (mild), 2 (moderate), 3 (severe), and 4 (life-threatening) |
Countries
United States
Participant flow
Pre-assignment details
The number enrolled (43) and number starting study (42) do not match because one patient never began study treatment due to an acute stroke prior to any study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Ofatumumab single-arm, open-label, interventional
ofatumumab: Weekly infusion for 8 weeks | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Ofatumumab |
|---|---|
| Age, Continuous | 64.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Lymphoma type Follicular | 28 Participants |
| Lymphoma type Marginal zone | 4 Participants |
| Lymphoma type Small lymphocytic | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 36 Participants |
| Region of Enrollment United States | 42 participants |
| Sex: Female, Male Female | 18 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 | 38 / 42 |
| serious Total, serious adverse events | 2 / 42 |
Outcome results
Primary
Efficacy: Complete Response Rate (CRR)
Evaluate clinical efficacy of ofatumumab in previously untreated indolent B-cell lymphomas, as measured by complete response rate (CRR). Complete response = all previously enlarged fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET)-positive lymph nodes regressed to normal size (\<=1.5 cm in greatest diameter)
Time frame: 1-month post-treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab | Efficacy: Complete Response Rate (CRR) | 9.5 percentage of patients |
Secondary
Overall Response Rate (ORR)
Evaluate clinical efficacy of ofatumumab in previously untreated indolent B-cell lymphomas, as measured by overall response rate (ORR). Overall response = Complete response (CR) + Partial response (PR) CR = all previously enlarged fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET)-positive lymph nodes regressed to normal size (\<=1.5cm in greatest diameter) PR = \>=50% decrease in SPD of up to six largest dominant masses, no increase in size of other nodes; FDG avid or PET positive before therapy, one or more nodes PET positive at previously involved site, or variably FDG avid or PET negative with regression at CT
Time frame: 1-month post-treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab | Overall Response Rate (ORR) | 52 percentage of patients |
Secondary
Progression-free Survival (PFS)
Percentage of patients with progression-free survival during 12 months post-treatment progression-free survival: patients live with the disease, but it does not get worse
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab | Progression-free Survival (PFS) | 86 percentage of patients |
Secondary
Toxicity: Infusion Reactions, Grade 3-4 Infections, and Neutropenia
Evaluate safety of ofatumumab monotherapy in this patient population Toxicities are graded 1 (mild), 2 (moderate), 3 (severe), and 4 (life-threatening)
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ofatumumab | Toxicity: Infusion Reactions, Grade 3-4 Infections, and Neutropenia | Infections (grade 3-4) | 1 Participants |
| Ofatumumab | Toxicity: Infusion Reactions, Grade 3-4 Infections, and Neutropenia | Infusion reactions (grade 1-2) | 22 Participants |
| Ofatumumab | Toxicity: Infusion Reactions, Grade 3-4 Infections, and Neutropenia | Infusion reactions (grade 3) | 7 Participants |
| Ofatumumab | Toxicity: Infusion Reactions, Grade 3-4 Infections, and Neutropenia | Neutropenia (grade 3-4) | 0 Participants |