Phase 2
N=43
Study of Iodine-131 Anti-B1 Antibody for Patients With Non Hodgkin's Lymphoma Who Have Previously Received Rituximab
Lymphoma, Non-Hodgkin
Bottom Line
View on ClinicalTrials.gov: NCT00996593 ↗Enrolled (actual)
43
Serious AEs
32.5%
Results posted
Jan 2012
Primary outcome: Primary: Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator — 26 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody (Tositumomab and Iodine I 131 Tositumomab) (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Apr 2001
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator |
26 | — |
| PRIMARY Number of Participants With Confirmed Complete Response (CR) as Assessed by the Investigator |
9 | — |
| PRIMARY Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) as Assessed by the Investigator |
15 | — |
| PRIMARY Number of Participants With Confirmed Partial Response (PR) as Assessed by the Investigator |
11 | — |
| PRIMARY Duration of Response for All Confirmed Responders (CR, CCR, or PR) as Assessed by the Investigator |
22.2 | — |
| PRIMARY Duration of Response for Confirmed CR as Assessed by the Investigator |
NA | — |
| PRIMARY Duration of Response for CR and CCR as Assessed by the Investigator |
NA | — |
| PRIMARY Duration of Response for All Confirmed Partial Responders as Assessed by the Investigator |
8.8 | — |
| PRIMARY Number of Participants With or Without (w/o) a Prior Response to Rituximab (Before Entry Into This Study) Who Were Classified as Responders in This Study |
12; 16 | 1.0 |
| PRIMARY Duration of Response for All Participants Classified as Responders With or Without a Prior Response to Rituximab |
18.6; 19.2 | 0.8 |
| PRIMARY Number of Participants With or Without (w/o) a Prior Response to Rituximab (Before Entry Into This Study) Who Were Classified as Having a Complete Response (CR) in This Study |
5; 4 | 1.0 |
| PRIMARY Duration of Response for All Participants With CR With or Without a Prior Response to Rituximab |
47.3; NA | 0.2 |
| PRIMARY Progression-free Survival for Participants With or Without a Prior Response to Rituximab |
13.0; 8.9 | 0.9 |
| PRIMARY Time to Progression of Disease or Death in All Responders, Participants With CR + CCR, and Participants With PR as Assessed by the Investigator |
10.4; NA; 9.2 | — |
| PRIMARY Overall Survival |
80 | — |
| SECONDARY Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants |
16; 15; 10; 5; 9; 7 | — |
| SECONDARY Number of Participants With the Indicated Type of Infection |
22; 18; 0; 0; 1; 5 | — |
| SECONDARY Number of Participants With an Infection for Which Anti-infectives Were Administered |
19; 3 | — |
| SECONDARY Number of Participants With Serious Adverse Events (SAE) Related to Study Drug |
2; 1; 1; 1; 1; 1 | — |
| SECONDARY Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations |
43.5; 43; 34.5; 43; 71; 74 | — |
| SECONDARY Nadir Values for ANC, a Hematologic Parameter |
1.2 | — |
| SECONDARY Nadir Values for Hemoglobin, a Hematologic Parameter |
11 | — |
| SECONDARY Nadir Values for Hematologic Parameters Platelets and WBC Count |
84.5; 2.3 | — |
| SECONDARY Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities |
16; 5; 10; 15 | — |
| SECONDARY Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities |
14; 28; 25; 11 | — |
Summary
This is a single-arm, open-label, multicenter study of Iodine I-131 Anti B1 Antibody (Tositumomab and Iodine I 131 Tositumomab) for treatment of non-Hodgkin's lymphoma (NHL) who were previously treated with rituximab antibody. Patients must have been treated with at least 4 doses of rituximab and have progressed during or following rituximab therapy.
Patients will undergo two dosing phases of study. In the first phase, termed the "dosimetric dose", patients will receive an infusion of unlabeled Anti-B1 Antibody (450 mg) over 70 minutes immediately followed by a 30-minute infusion of Anti-B1 Antibody (35 mg) which has been radiolabeled with 5 mCi of Iodine-131. Whole body gamma camera scans will be obtained on Day 0; Day 2, 3, or 4; and Day 6 or 7 following the dosimetric dose. Using the dosimetric data from three imaging timepoints, a patient-specific dose of Iodine-131 will be calculated to deliver the desired total body dose of radiotherapy. In the second phase, termed the "therapeutic dose", patients will receive a 70-minute infusion of unlabeled Anti-B1 Antibody (450 mg) immediately followed by a 30-minute infusion of 35 mg Anti-B1 Antibody labeled with a patient-specific dose of Iodine-131 to deliver a whole body dose of 75 cGy to patients with no hematologic risk factors. Patients who have platelet counts of 100,001-149,999 cells/mm3 will receive 65 cGy and patients who are obese will be dosed based upon 137% of their lean body mass. Patients will be treated with either saturated solution potassium iodide (SSKI), Lugol's solution, or potassium iodide tablets starting at least 24 hours prior to the first infusion of the Iodine-131 Anti-B1 Antibody (i.e., dosimetric dose) and continuing for 14 days following the last infusion of Iodine-131 Anti-B1 Antibody (i.e., therapeutic dose).
The endpoints of the study are to determine the response rate, complete response rate, duration of response, and time to progression or death, based on both a Masked Independent Randomized Radiographic and Oncologic Review (MIRROR) panel and the Investigators, and the Investigators' assessment of safety and survival of survival of Iodine-131 Anti-B1 Antibody therapy in NHL patients who have previously been treated with rituximab.
Eligibility Criteria
Inclusion Criteria
- Patients must have a histologically confirmed diagnosis of low-grade non-Hodgkin's B-cell lymphoma according to International Working Formulation.
- Patients must have evidence that their tumor tissue expresses the CD20 antigen. Immunoperoxidase stains of paraffin-embedded tissue showing positive reactivity with L26 antibody or immunoperoxidase stains of frozen tissue showing positive reactivity with Anti-B1 Antibody or evidence of CD20 positivity by flow cytometry are acceptable evidence of CD20 positivity.
- Patients must have been treated with at least 4 doses of rituximab at any time and failed to achieve an objective response (CR, CCR, PR) or relapse/progressed during treatment or following the completion of rituximab therapy.
- Patients must have a performance status of at least 60% on the Karnofsky Scale and an anticipated survival of at least 3 months.
- Patients must have an absolute granulocyte count >1500 cells/mm3 (US) and a platelet count >100,000 cells/mm3 (US) within 14 days of study entry. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products.
- Patients must have adequate renal function (defined as serum creatinine 3500 cGy.
- Patients who are HAMA positive.
- Patients who are concurrently receiving either approved or non-approved (through another protocol) anti-cancer drugs or biologics.
Data sourced from ClinicalTrials.gov (NCT00996593). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.