Ibritumomab Tiuxetan for Treatment of Non-Follicular CD20+ Indolent Lymphomas
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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and biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Zevalin
.3 mCi IV Over 10 Minutes x 1 Day
Other Names:
Drug: Rituximab
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
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
-
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).
-
Signed informed consent
-
Age >/= 18 years
-
Expected survival >/= 3 months
-
Pre-study Zubrod performance status of 0, 1, or 2
-
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/mm3; (b) Platelet counts >/= 100,000/mm3.
-
Female patients who are not pregnant or lactating
-
Men and women of reproductive potential who are following accepted birth control methods (as determined by the treating physician)
-
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
-
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.)
-
Patient should have at least one lesion measuring >/= 2 cm in a single dimension.
Exclusion Criteria:
-
Prior myeloablative therapies with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell (PBSC) rescue.
-
Platelet count< 100,000 cells/mm^3.
-
Presence of hypocellular bone marrow.
-
Patients with history of failed stem cell collection.
-
Prior radioimmunotherapy
-
Presence of Central Nervous System (CNS) lymphoma
-
Patients with HIV.
-
Patients with pleural effusion
-
Patients with abnormal liver function: total bilirubin > 2.0 mg/dL
-
Patients with abnormal renal function: serum creatinine > 2.0 mg/dL
-
Patients who have received prior external beam radiation therapy to > 25% of active bone marrow (involved field or regional)
-
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.
-
Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives
-
Major surgery, other than diagnostic surgery, within four weeks
-
Evidence of transformation in the latest biopsy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UT MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- Biogen
Investigators
- Principal Investigator: Felipe Samaniego, MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2005-0571
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Ibritumomab Tiuxetan + Rituximab |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 6 |
| COMPLETED | 5 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Ibritumomab Tiuxetan + Rituximab |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 6 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
67.5
|
| Sex: Female, Male (Count of Participants) | |
| Female |
5
83.3%
|
| Male |
1
16.7%
|
| Region of Enrollment (participants) [Number] | |
| United States |
6
100%
|
Outcome Measures
| Title | Objective Response Rate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant did not receive treatment and was excluded from analysis. |
| Arm/Group Title | Ibritumomab Tiuxetan + Rituximab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 5 |
| Number [proportion of participants] |
0.8
13.3%
|
Adverse Events
| Time Frame | 4 years and 4 months | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Ibritumomab Tiuxetan + Rituximab | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| Ibritumomab Tiuxetan + Rituximab | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Ibritumomab Tiuxetan + Rituximab | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/5 (20%) | |
| Blood and lymphatic system disorders | ||
| Neutropenia | 1/5 (20%) | |
Other (Not Including Serious) Adverse Events |
||
| Ibritumomab Tiuxetan + Rituximab | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | |
| Blood and lymphatic system disorders | ||
| Thrombocytopenia | 2/5 (40%) | |
| Neutropenia | 2/5 (40%) | |
| General disorders | ||
| Fatigue | 1/5 (20%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Felipe Samaniego, MD / Associate Professor |
|---|---|
| Organization | The University of Texas (UT) MD Anderson Cancer Center |
| Phone | |
| CR_Study_Registration@mdanderson.org |
- 2005-0571