Lymphoma
Conditions
Keywords
Indolent Lymphoma, Extranodal Marginal, Nodal Marginal Zone, Splenic Marginal, MALT Type, Zevalin, Ibritumomab Tiuxetan, Rituximab
Brief summary
Primary Objective: * Overall Response Rate (ORR). Secondary Objectives: * The Duration of Response (DR) and Time to Treatment Progression (TTP) in all patients and in the responders. * Complete Responses (CR)/Complete Responses unconfirmed (CRu), and Partial Responses (PR). * Time to next anticancer therapy (TTNT).
Detailed description
\^90 Y Ibritumomab tiuxetan and rituximab are both designed to attach to lymphoma cells, causing them to die. Before you can start treatment on this study, you will have what are called screening tests. These tests will help the doctor decide if you are eligible to take part in this study. You will have a physical exam. Your blood (about 2 to 3 teaspoons) and urine will be collected for routine tests. You will have a chest x-ray and computerized tomography (CT) scans of the neck, chest, abdomen, and pelvis. You will have a bone marrow aspirate and biopsy performed. To collect a bone marrow aspirate and biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. Women who are able to have children must have a negative blood pregnancy test. The study doctors will first make sure that your disease has not spread too much and is not too severe to require immediate treatment with chemotherapy before you can begin treatment on this study. If you are found to be eligible to take part in this study, you will be given Benadryl (diphenhydramine) by vein, and you will be given Tylenol (acetaminophen) by mouth before each dose of rituximab. This is done to help decrease the risk of developing side effects of rituximab. You will then receive 1 dose of rituximab by vein over 6 to 8 hours on Day 1 of treatment. After treatment with rituximab, you will then be given a radioactive antibody, \^111 In Ibritumomab tiuxetan (this is a radioactive agent that binds to rituximab to help with imaging exams), by vein over about 10 minutes. This is so researchers can use a special camera to see where the drug is in your body. You will have imaging performed (with the special camera) on Day 1 and on either Day 2 or Day 3. On Day 8, you will receive a second dose of rituximab. This will then be followed by a dose \^90 Y Ibritumomab tiuxetan of given by vein over 10 minutes. This completes the treatment. If you experience intolerable side effects while on this study, you may be removed from this study. The study doctor will then offer other treatment options to you. For your follow-up, you will have blood (about 2 tablespoons) drawn once a week for the first 3 months, then every 3 months for 1 year, and then every 4 months for the second year. At these visits, you may also have CT scans, x-rays, and bone marrow biopsies and aspirates performed, if needed. This is an investigational study. \^90 Y Ibritumomab tiuxetan and rituximab have been approved by the FDA for the treatment of indolent B-cell lymphoma. Up to 35 patients will take part in this multicenter study. Up to 15 will be enrolled at M. D. Anderson.
Interventions
DRUGZevalin
.3 mCi IV Over 10 Minutes x 1 Day
DRUGRituximab
250 mg/m\^2 IV Over 6 to 8 Hours
DRUG^111 In Ibritumomab Tiuxetan
1.6 mg IV Over 10 Minutes x 1 Day
Sponsors
Biogen
M.D. Anderson Cancer Center
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
1. No anti-cancer therapy for three weeks (six weeks if Rituximab, nitrosourea or Mitomycin C) prior to study initiation, and fully recovered from acute toxicities associated with prior surgery, radiation treatments, chemotherapy, or immunotherapy. 2. Previously treated patients with a histology of refractory/relapsed indolent lymphomas including: (a) Extranodal marginal lymphoma of MALT type; (b) Nodal Marginal zone B-cell lymphoma (+/- monocytoid cells); (c) Splenic marginal B-cell lymphoma (+/- villous lymphocytes). 3. Signed informed consent 4. Age \>/= 18 years 5. Expected survival \>/= 3 months 6. Pre-study Zubrod performance status of 0, 1, or 2 7. Acceptable hematologic status within two weeks prior to patient registration, including: (a) Absolute neutrophil count (\[segmented neutrophils + bands\] \* total white blood count (WBC)) \>/= 1,500/mm\^3; (b) Platelet counts \>/= 100,000/mm\^3. 8. Female patients who are not pregnant or lactating 9. Men and women of reproductive potential who are following accepted birth control methods (as determined by the treating physician) 10. Patients previously on Phase II drugs if no long-term toxicity is expected, and the patient has been off the drug for eight or more weeks with no significant post treatment toxicities observed 11. Patients determined to have \< 25% bone marrow involvement with lymphoma within six weeks of registration (define measurement of a bone marrow aspirate or biopsy) (This criteria must be strictly met for adequate patient safety.) 12. Patient should have at least one lesion measuring \>/= 2 cm in a single dimension.
Exclusion criteria
1. Prior myeloablative therapies with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell (PBSC) rescue. 2. Platelet count\< 100,000 cells/mm\^3. 3. Presence of hypocellular bone marrow. 4. Patients with history of failed stem cell collection. 5. Prior radioimmunotherapy 6. Presence of Central Nervous System (CNS) lymphoma 7. Patients with HIV. 8. Patients with pleural effusion 9. Patients with abnormal liver function: total bilirubin \> 2.0 mg/dL 10. Patients with abnormal renal function: serum creatinine \> 2.0 mg/dL 11. Patients who have received prior external beam radiation therapy to \> 25% of active bone marrow (involved field or regional) 12. Patients who have received short-acting growth factor support (Leukine, Neupogen, Procrit) within 2 weeks prior to treatment or long-acting growth-factor support (Aranesp), Neulasta) within 4 weeks prior to treatment. 13. Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives 14. Major surgery, other than diagnostic surgery, within four weeks 15. Evidence of transformation in the latest biopsy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Evaluation 4 weeks after administration of Zevalin up to 3 years | Objective response rate (ORR) = number of participants out of all participating with Complete Response (CR) + Partial Response (PR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. Response assessed by magnetic resonance imaging (MRI) or computed tomography (CT) scans, every 3 months for the first year and every 6 months up to 3 years following. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: April 13, 2006 to November 8, 2007. All participants recruited in medical clinic at UT MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Ibritumomab Tiuxetan + Rituximab Rituximab 250 mg/m² intravenous (IV) Days 1 and 8, 111In Ibritumomab Tiuxetan (5mCi of 111In, 1.6 mg of Ibritumomab Tiuxetan) IV (over 10 minutes) on Day 1; and 90Y Ibritumomab Tiuxetan 0.3 or 0.4 mCi/kg IV (over 10 minutes) on Day 8 after the Day 8 of Rituximab. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Ibritumomab Tiuxetan + Rituximab |
|---|---|
| Age Continuous | 67.5 years |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Objective Response Rate
Objective response rate (ORR) = number of participants out of all participating with Complete Response (CR) + Partial Response (PR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. Response assessed by magnetic resonance imaging (MRI) or computed tomography (CT) scans, every 3 months for the first year and every 6 months up to 3 years following.
Time frame: Evaluation 4 weeks after administration of Zevalin up to 3 years
Population: One participant did not receive treatment and was excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibritumomab Tiuxetan + Rituximab | Objective Response Rate | 0.8 proportion of participants |