Phase 1
N=59
Study of Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas and Extended Study to Determine the Safety and Efficacy of Coulter Clone® 131Iodine-B1 Radioimmunotherapy of Advanced Non-Hodgkin's Lymphoma
Lymphoma, Non-Hodgkin
Bottom Line
View on ClinicalTrials.gov: NCT01536561 ↗Enrolled (actual)
59
Serious AEs
32.9%
Results posted
Mar 2012
Primary outcome: Primary: Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) — 6; 1; 2; 4 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas (Tositumomab and Iodine I 131 Tositumomab) (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jul 1997
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) |
6; 1; 2; 4; 8; 1 | — |
| PRIMARY Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose) |
1; 1; 2; 1; 1; 2 | — |
| PRIMARY Maximum Tolerated Dose (MTD) of TST/I 131 TST Evaluated in the Study |
75; 45 | — |
| PRIMARY Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) |
477.68; 1074.27; 607.57; 261.26; 192.35; 242.59 | — |
| SECONDARY Tumor/Organ Dosimetry at the Indicated Predoses of 475 mg, 95 mg, and 0 mg (Initial Treatment) |
411.5; 1023.04; 451.77; 1177.3; 624; 1073.75 | — |
| SECONDARY Number of Participants (Par.) With the Indicated Response as Assessed by the Investigator |
20; 4; 0; 0; 22; 4 | — |
| SECONDARY Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator |
20; 4; 0; 0; 9; 3 | — |
| SECONDARY Duration of Response for All Unconfirmed Responders (CR, CCR, or PR) as Assessed by the Investigator |
8.5; 7.7 | — |
| SECONDARY Time to Progression of Disease or Death |
5.7; 4.9 | — |
| SECONDARY Overall Survival |
46.4; 45.0 | — |
| SECONDARY Half-life: Initial Half-life (t1/2 Alpha) and Terminal Half-life (t1/2 Beta) of I 131 TST for the Antibody Predose Levels of 0 mg, 95 mg, and 475 mg |
6.2; 6.0; 6.7; 63.2; 72.6; 84.5 | — |
| SECONDARY Clearance (CL) of I 131 TST for the Indicated Antibody Predose Levels |
205; 99.4; 72.1 | — |
| SECONDARY Area Under the Concentration Time Curve (AUC) of I 131 TST for the Indicated Antibody Predose Levels |
0.838; 1.42; 1.68 | — |
| SECONDARY Maximum Blood Concentration (Cmax) of I 131 TST for the Indicated Antibody Predose Levels |
0.0164; 0.0190; 0.0194 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of I 131 TST for the Indicated Antibody Predose Levels |
13.0; 7.74; 7.08 | — |
| SECONDARY Number of Participants Who Developed Human Anti-mouse Antibodies (HAMA Postivitiy) After Receiving Tositumomab |
9; 2; 49; 2 | — |
| SECONDARY Time to HAMA Positivity From the First Dosimetric Dose (Time From Baseline [Dosimetric Dose] to the First Reported Presence of HAMA) |
15.0; 1271 | — |
| SECONDARY Number of Participants With the Indicated Type of Infection |
24; 2; 35; 12; 6; 1 | — |
| SECONDARY Time to Nadir for the Indicated Hematologic Laboratory Parameters |
44.5; 44.5; 34.0; 49.5; 34.0; 41.0 | — |
| SECONDARY Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters |
79.0; 74.0; 42.0; 38.5; 57.0; 39.0 | — |
| SECONDARY Nadir Values for the Hematologic Parameters ANC, Platelets, and WBC Count |
1.0; 1.3; 74.0; 79.5; 2.7; 3.3 | — |
| SECONDARY Nadir Values for Hemoglobin, a Hematologic Parameter |
10.9; 11.7 | — |
Summary
Phase I/II, single-center, dose-escalation study of the safety, pharmacokinetics, dosimetry, and efficacy of TST/I-131 TST for the treatment of patients with chemotherapy-refractory or resistant low-grade, intermediate-grade, or high-grade B-cell lymphoma. Subjects received 1 to 3 dosimetric doses followed by a therapeutic dose of TST/I-131 TST. Study BEX104526 was a follow-up study of the long-term safety and efficacy data from the surviving patients who completed at least 2 years of follow-up following administration of TST/I 131 TST on Study BEX104728.
Dosimetric dose: Subjects received 1 to 3 dosimetric doses of TST/I-131 TST, followed by a therapeutic dose of TST/I-131 TST. Subjects received various doses of unlabeled TST (0, 95 or 475 mg) to determine the dose of unlabeled TST that optimized the radiation dose delivered to the tumor by TST/I-131 TST. The unlabeled TST was followed by 5 milliCurie (mCi) of I-131 TST. Serial whole body sodium iodide scintillation probe counts were obtained daily, for at least 5 days, in order to determine the rate of whole body clearance of radioactivity (residence time). The residence time was used to determine the radioactive clearance for the subject and the activity (in mCi) of I-131 required to deliver the desired TBD of radiation during the therapeutic dose. Because 475 mg was determined to be the optimal pre-dose of TST in the first subjects entered, the last 34 subjects received a single dosimetric dose that was preceded by an infusion of 475 mg of TST.
Therapeutic dose: Groups of 3-6 subjects were enrolled at successively higher whole-body radiation dose levels beginning at a total body dose (TBD) of 25 centiGray (cGy). The TBD of each subsequent dose level was escalated by 10 cGy. Subjects who had undergone bone marrow transplantation (BMT) underwent a separate dose escalation (10 cGy TBD increase per dose level) beginning at a TBD level of 65 cGy. The MTD was defined as the highest dose level at which 0/3 or 1/6 subjects experienced dose-limiting toxicity (DLT). DLT was defined as follows:
Any Grade 4 hematologic toxicity (National Cancer Institute [NCI] criteria) lasting greater than 7 days, or Any Grade 3 hematologic toxicity lasting greater than 2 weeks, or Any Grade 3 or 4 nonhematologic toxicity Redosing. Subjects who achieved tumor regression were considered for re-dosing, using the original therapeutic dose of TST/I-131 TST, at the time the tumor was no longer shrinking in an attempt to upgrade their response.
Retreatment. Subjects who achieved partial (PR) or complete response (CR) were considered for retreatment following relapse of their NHL, if progression occurred ≥6 weeks following the therapeutic dose. The original therapeutic dose of TST/I-131 TST was given unless a grade 2 or greater toxicity had been encountered, in which case a reduced dose was administered for the repeat therapeutic dose.
Eligibility Criteria
Inclusion Criteria
- Subjects had histologically-confirmed NHL.
- Subjects with low-, intermediate-, or high-grade histologies, according to the International Working Formulation.
- Subjects had relapsed after or had failed to respond to at least 1 prior chemotherapy regimen.
- Subjects had evidence that their tumor tissue expressed the CD20 antigen.
Exclusion Criteria
- ≥25% bone marrow involvement.
- Absolute granulocyte count ≥1500 cells/mm3 or platelet count ≤100,000 platelets/mm3.
- Creatinine ≥2.0 mg/dL, bilirubin ≥2.0 mg/dL.
- Cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks of study entry.
- Active infection, collagen vascular disease, vasculitis, glomerulonephritis, New York Heart Association class II or IV heart disease and/or serious illness.
- Prior external beam radiation therapy such that the maximum tolerated dose level for any normal organ would be exceeded by additional irradiation.
- Pregnancy.
- Allergy to iodine or previous sensitization to mouse protein as documented by positive anti-mouse antibody ELISA test.
- Known brain metastases.
Data sourced from ClinicalTrials.gov (NCT01536561). 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.