Lymphoma
Conditions
Brief summary
The purpose of this study is to obtain safety and efficacy data using Bexxar in patients with relapsed/refractory diffuse large cell Non-Hodgkin's lymphoma (DLCL).
Detailed description
There is a lack of efficacious treatment options for patients with relapsed/refractory diffuse large cell Non-Hodgkin's lymphoma (DLCL) who are not appropriate candidates for stem cell transplantation. DLCL is a relatively radiosensitive disease and patients with DLCL have been reported to respond to anti-CD20 monoclonal antibody (MAB) therapy. Therefore, radioimmunotherapy targeting CD20 is a rational and promising therapeutic approach for this patient population. This study evaluated if Bexxar is safe and efficacious for diffuse large cell Non-Hodgkin's lymphoma.
Interventions
DRUGBexxar
Bexxar is a radioimmunotherapeutic drug, an antibody that specifically attaches to the CD20 antigen, which is present on the surfaces of B cells and B cell lymphoma cells. The radioactive isotope then gives off radiation, which kills the cells. Bexxar will be administered to provide the following patient-specific radiotherapy: * Platelet count of 150,000/mm³ = 75 cGy * Platelet count ≥ 100,000/mm³ but \< 150,000/mm³ = 65 cGy
DRUGAcetaminophen
As premedication 30 to 60 minutes before antibody infusion; 650 mg, oral. Used to as to relieve pain
DRUGDiphenhydramine
As premedication 30 to 60 minutes before antibody infusion; 50 mg, oral. Used to prevent inflammation or allergic reactions
Administered to prevent thyroid blockage 130 mg orally 3 times a day,
Sponsors
Corixa Corporation
GlaxoSmithKline
Susan Knox
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
* Histologically-confirmed, diffuse large cell lymphoma (DLCL), CD20+ B-cell non-Hodgkin lymphoma (NHL) who have relapsed after chemotherapy or are chemotherapy resistant, without prior history of low grade NHL. The patient must have failed at least one chemotherapy regimen containing an anthracycline or equivalent chemotherapeutic agent. * No anticancer treatment for three weeks prior to the treatment dose of Bexxar (6 weeks if Rituximab, nitrosourea or Mitomycin C) * Fully recovered from all toxicities associated with prior surgery, radiation, chemotherapy or immunotherapy * An Institutional Review Board (IRB)-approved signed informed consent * Age 19 years or older * Prestudy Karnofsky Performance Status of ≥ 70% * Absolute neutrophil count (ANC) ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hct \> 30% * Hgb \> 9.0 gm% * Bilirubin ≤ 2.0 * Creatinine ≤ 2.0 * Bone marrow involvement with lymphoma less than 25% (bilateral bone marrow) within 6 weeks of enrollment * Acceptable birth control method for men and women * Female patients who are not pregnant * Not lactating
Exclusion criteria
* Prior myeloablative therapies with bone marrow transplantation or peripheral stem cell rescue * Platelet count \< 100,000/mm³ * Hypocellular bone marrow (≤ 15% cellularity) * Marked reduction in bone marrow precursors of one or more cell lines * History of failed stem cell collection * Prior treatment with Fludarabine * Prior radioimmunotherapy * Presence of central nervous system (CNS) lymphoma * Patients with known HIV or AIDS-related lymphoma * Patients with evidence of myelodysplasia on bone marrow biopsy * Patients who have received prior external beam radiation therapy to more than 25% of active bone marrow * Patients who have received filgrastim or sargramostim therapy within 3 weeks prior to treatment * Pregnant * Lactating * Presence of human anti-mouse antibody (HAMA) reactivity in patients with prior exposure to murine antibodies or proteins * Serious nonmalignant disease or infection, which, in the opinion of the investigator, would compromise other protocol objectives * Another primary malignancy (other than squamous cell and basal cell carcinoma of the skin, in situ carcinoma of the cervix, or treated prostate cancer with stable prostate specific antigen levels) for which the patients has not been disease-free for at least 3 years * Major surgery, other than diagnostic surgery, within 4 weeks * Patients with pleural effusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response Rate | 6 years | Clinical response rate for all participants, reported as the sum of the numbers of patients achieving complete response (CR, complete disappearance of all lesions); functional CR (fCR, minimal residual disease but clear of disease by positron emission tomography (PET)-scan); or partial response (PR, ≥ decrease in size of lesions and negative for active disease by PET-scan). Progressive disease (PD, advancing cancer) or stable disease (not CR, fCR, or PD) not included as Clinical Response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | 1.5 months; 3 months; 6 months; or Not Progressed | Time of disease progression reported as the number of subjects experiencing disease progression at the time point of progression. |
| Overall Survival (OS) Rate | 6 years | Overall survival reported as the percentage of participants (less lost-to-follow-up) surviving at 6 years. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bexxar Phase 2 study in patients with relapsed/refractory DLCL who were not candidates for transplantation. Bexxar was dosed as per the FDA approved regimen for other indications. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Bexxar |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 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 | 7 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 9 / 9 |
Outcome results
Primary
Clinical Response Rate
Clinical response rate for all participants, reported as the sum of the numbers of patients achieving complete response (CR, complete disappearance of all lesions); functional CR (fCR, minimal residual disease but clear of disease by positron emission tomography (PET)-scan); or partial response (PR, ≥ decrease in size of lesions and negative for active disease by PET-scan). Progressive disease (PD, advancing cancer) or stable disease (not CR, fCR, or PD) not included as Clinical Response.
Time frame: 6 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bexxar | Clinical Response Rate | Clinical Response | 2 participants |
| Bexxar | Clinical Response Rate | Complete Response (CR) | 0 participants |
| Bexxar | Clinical Response Rate | Functional CR | 1 participants |
| Bexxar | Clinical Response Rate | PR | 1 participants |
| Bexxar | Clinical Response Rate | SD | 6 participants |
| Bexxar | Clinical Response Rate | PD | 1 participants |
Secondary
Overall Survival (OS) Rate
Overall survival reported as the percentage of participants (less lost-to-follow-up) surviving at 6 years.
Time frame: 6 years
Population: 1 of the 9 study participants was lost-to-follow-up, and did not contribute data to this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bexxar | Overall Survival (OS) Rate | 37.5 percentage of participants |
Secondary
Time to Progression (TTP)
Time of disease progression reported as the number of subjects experiencing disease progression at the time point of progression.
Time frame: 1.5 months; 3 months; 6 months; or Not Progressed
Population: 1 of the 9 study participants was lost-to-follow-up, and did not contribute data to this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bexxar | Time to Progression (TTP) | 1.5 months | 1 participants |
| Bexxar | Time to Progression (TTP) | 3 months | 2 participants |
| Bexxar | Time to Progression (TTP) | 6 months | 2 participants |
| Bexxar | Time to Progression (TTP) | Not Progressed | 3 participants |