- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01868035
Iodine-131 Anti-B1 Antibody Consolidation for Patients With Non-Hodgkin's Lymphoma Following First-line CHOP
Phase II Multicenter Study of Iodine-131 Anti-B1 Antibody Consolidation For Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma Following First-line CHOP
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a phase II, open-label, multicenter study of Iodine-131 Anti-B1 Antibody consolidation for 20 patients with diffuse large B-cell non-Hodgkin's lymphoma (NHL) achieving a partial response (PR), an unconfirmed complete response (CRu), or complete response (CR) following 6-8 cycles of first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Although the majority of patients entered in previous Iodine-131 Anti-B1 Antibody studies had low-grade or transformed low-grade NHL, 15 patients with de novo intermediate-grade NHL have been treated. Patients will undergo two dosing phases of Iodine-131 Anti-B1 Antibody.
In the first phase, termed the "dosimetric dose," patients will receive an infusion of unlabeled Anti-B1 Antibody (450 mg) over 60 minutes followed by a 30-minute infusion (including a 10-minute flush) of Anti-B1 Antibody (35 mg) that contains 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 the three imaging time points, 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 60-minute infusion of unlabeled Anti-B1 Antibody (450 mg) followed by a 30-minute infusion (including a 10-minute flush) of 35 mg Anti-B1 Antibody labeled with a patient-specific dose of Iodine-131 calculated to deliver a 75 cGy total body radiation dose . Patients who have platelet counts of 100,000-149,999 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 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 primary endpoint of this study is to determine the incidence of Grade IV hematologic toxicity following Iodine-131 Anti-B1 Antibody consolidation for patients with diffuse large B-cell NHL who achieved a response (PR, CRu, CR) following first-line CHOP chemotherapy. The secondary efficacy endpoints are to determine the complete response rate, duration of response, duration of complete response, progression-free survival, and time to treatment failure. The pharmacokinetic endpoint is to determine the total body residence time following the dosimetric dose. The secondary safety endpoints are to determine the incidence of adverse experiences, hematologic toxicity (e.g., nadir, time to nadir, and time to recovery), use of supportive care, percent of patients converting to human anti-murine antibody (HAMA) positivity, and survival.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- male or female subjects age 18 to 80 years, inclusive, with any International Prognostic Index score; treated with 6 or more cycles of first-line CHOP chemotherapy and achieved a PR, CRu, or CR
- de novo diffuse large B-cell NHL according to the REAL classification; Ann Arbor stage III, stage IV, or bulky stage II disease (any mass ≥10 cm in diameter)
- less than an average of 25% of the intratrabecular marrow space involved by NHL in bilateral bone marrow biopsy specimens or <10% involvement with NHL from unilateral bone marrow biopsy; tumor tissue expressing the CD20 antigen
- ≥60% performance status on the Karnofsky Performance Scale and an anticipated survival of at least 3 months
- absolute neutrophil count (ANC) ≥1500 cells/mm3 and platelet count ≥100,000/mm3
- adequate renal function (serum creatinine <1.5 × upper limit of normal [ULN]) and hepatic function (total bilirubin ≤2.0 × ULN and aspartate aminotransferase <5 × ULN)
Exclusion Criteria:
- prior radiation, prior biological therapy, or prior chemotherapy other than first-line CHOP
- active bilateral obstructive hydronephrosis
- New York Heart Association class III or IV heart disease or other serious illness
- prior malignancy other than lymphoma (except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which they had been disease-free for >5 years)
- human immunodeficiency virus infection
- HAMA positive
- brain or leptomeningeal metastases at any time since diagnosis
- active infection requiring intravenous anti-infectives
- pregnant or breastfeeding
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Single Arm
tositumomab and iodine I-131 tositumomab
|
Subjects received the following treatments of TST/I-131 TST by intravenous (IV) infusion: Dosimetric Dose: 450 mg of TST infused over 1 hour immediately followed by 35 mg of TST labeled with 5 milliCuries (mCi) of I 131 infused over 30 minutes. Therapeutic Dose: 7 to 14 days after the dosimetric dose, 450 mg of TST infused over 60 minutes, immediately followed by 35 mg of TST labeled with the subject-specific mCi activity of I 131 needed to deliver a total body dose of 75 centiGrays (cGy), infused over 30 minutes for subjects with a platelet count of 150,000/mm3. Subjects with platelet counts of 100,000 to 149,999/mm3 received 65 cGy, and obese subjects were dosed based upon 137% of their calculated lean body mass.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With the Indicated Grade 4 Hematology Toxicities Following Iodine-131 Anti-B1 Antibody
Time Frame: From Baseline until Week 25 and follow-up (up to 130 months)
|
Hematology parameter grades were summarized according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 2.0.
Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling; Grade 5, death.
Data are presented for those participants who experienced Grade 4 toxicities.
Grade 4 hematological toxicities included absolute neutrophil count (ANC) (calculated) <1000 cells/millimeters cubed (mm^3), white blood cells (WBC) <2000 cells/mm^3, platelets <50000 cells/mm^3, and hemoglobin < 8.0 grams/deciliter.
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From Baseline until Week 25 and follow-up (up to 130 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants (Par.) With Confirmed (Con.) Complete Response (CR) Confirmed, Confirmed Complete Response Unconfirmed (CRu), Confirmed Partial Response (PR), Relapse Disease (RD), and Progressive Disease (PD)
Time Frame: From Baseline until Week 25 and follow-up (up to 130 months)
|
CR is defined as the complete disappearance of all detectable clinical/radiographic evidence of disease, the disappearance of all disease-related symptoms if present before therapy, and normalization of biochemical abnormalities definitely assignable to non Hodgkin's lymphoma (NHL).
PR is defined as a >=50% decrease in the sum of perpendicular diameters (SPPD) of splenic and hepatic nodules determined at Baseline.
SD is defined as less than a PR, but not PD, which is defined as a >=50% increase from nadir in SPPD of splenic and hepatic nodules or the appearance of any new lesion during or at the end of therapy that was >1.5 centimeters (cm) by radiographic evaluation or >1.0 cm by physical examination.
RD is defined as the appearance of any new lesion or an increase of >= 50% in the size of nodules.
Confirmed response requires that the same or better response be confirmed by two consecutive post-therapy response evaluations at least 4 weeks apart.
|
From Baseline until Week 25 and follow-up (up to 130 months)
|
Duration of Response and Duration of Confirmed Complete Response
Time Frame: From Baseline until Week 25 and follow-up (up to 130 months)
|
Duration of response for all participants with confirmed PR, confirmed CRu, or confirmed CR is defined as the time from the first documented response to the first documented progression.
CR is defined as the complete disappearance of all detectable clinical/radiographic evidence of disease, the disappearance of all disease-related symptoms if present before therapy, and the normalization of biochemical abnormalities definitely assignable to NHL.
PR is defined as a >=50% decrease in the sum of the perpendicular diameters (SPPD) of splenic and hepatic nodules determined at Baseline.
PD is defined as a >=50% increase from nadir in SPPD of splenic and hepatic nodules or the appearance of any new lesion during or at the end of therapy that was >1.5 centimeters (cm) by radiographic evaluation or >1.0 cm by physical examination.
Confirmed response requires that the same or better response be confirmed by two consecutive post-therapy response evaluations at least 4 weeks apart.
|
From Baseline until Week 25 and follow-up (up to 130 months)
|
Progression-free Survival (PFS)
Time Frame: From Baseline until Week 25 and follow-up (up to 130 months)
|
PFS is defined as the time from the start of treatment to the first documented progression or death.
Duration measures were calculated using Kaplan-Meier techniques.
Disease progression was based on radiographic or photographic evidence, and assessments were made by the investigator.
PD is defined as a >=50% increase from nadir in SPPD of splenic and hepatic nodules or the appearance of any new lesion during or at the end of therapy that was >1.5 centimeters (cm) by radiographic evaluation or >1.0 cm by physical examination.
|
From Baseline until Week 25 and follow-up (up to 130 months)
|
Time to Treatment Failure (TTF)
Time Frame: From Baseline until Week 25 and follow-up (up to 130 months)
|
TTF is defined as the time from the start of treatment to the first occurrence of treatment withdrawal, decision to seek additional therapy, study removal, disease progression, or death.
Duration measures were calculated using Kaplan-Meier techniques.
Disease progression was based on radiographic or photographic evidence, and assessments were made by the investigator.
PD is defined as a >=50% increase from nadir in SPPD of splenic and hepatic nodules or the appearance of any new lesion during or at the end of therapy that was >1.5 centimeters (cm) by radiographic evaluation or >1.0 cm by physical examination.
|
From Baseline until Week 25 and follow-up (up to 130 months)
|
Total Body Residence Time (TBRT)
Time Frame: From Baseline until Week 25 and follow-up (up to 130 months)
|
TBRT is the time at which the activity of infusion is 37% of that at time zero.
Whole body images from anterior and posterior gamma camera scans were collected to assess dosimetry.
The assessment of organ dosimetry required gamma camera scans from at least 4 time points.
Nuclear medicine reviewers conducted a visual examination of the gamma camera scans and calculated the TBRTs.
Residence time is calculated from the rate of total body clearance of iodine I-131 radioactivity during the dosimetric dose.
Residence time is a measure of how long the drug resides in the body.
|
From Baseline until Week 25 and follow-up (up to 130 months)
|
Number of Participants With an Adverse Experience, Including Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From Baseline until Week 25 and follow-up (up to 130 months)
|
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and does not necessarily have to have a casual relationship with this treatment.
An AE can therefore be any unfavorable and unintended sign, symptom, or significant worsening of a pre-existing sign or symptom, or disease temporally associated with the use of a medicinal product.
An SAE is defined as any experience occurring at any dose that results in the following outcomes: death, a life-threatening adverse experience, in-patient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
See the SAE/AE module for a complete list of SAEs/AEs.
|
From Baseline until Week 25 and follow-up (up to 130 months)
|
Time to Recovery From the Indicated Hematology Toxicities
Time Frame: From Baseline until Week 25 and follow-up (up to 130 months)
|
Hematology toxicities included ANC (calculated), WBC count, platelet count, and hemoglobin.
Time to recovery to Baseline grade for participants with Grade 0 toxicity at Baseline was defined as the time from the date of the last administration of study drug to the first post-nadir date with Grade 0 toxicity, with no other Grade 1-4 toxicities recorded during the next week.
For participants with a Grade 1-4 toxicity at Baseline, time to recovery was defined as the time from the last administration of study drug to the first post-nadir date with a Baseline grade or better, with no other higher grade toxicities recorded during the next week.
For participants with a nadir grade less than or equal to the Baseline grade, the time to recovery to the Baseline grade equaled the time to nadir.
|
From Baseline until Week 25 and follow-up (up to 130 months)
|
Nadir for the Indicated Hematology Toxicities
Time Frame: From Baseline until Week 25 and follow-up (up to 130 months)
|
Hematology toxicities included ANC (calculated), hemoglobin, platelet count, WBC count.
Nadir is defined as lowest counts that the cells reach after chemotherapy.
|
From Baseline until Week 25 and follow-up (up to 130 months)
|
Time to Nadir for the Indicated Hematology Toxicities
Time Frame: From Baseline until Week 25 and follow-up (up to 130 months)
|
Hematology toxicities included ANC (calculated), WBC count, platelet count, and hemoglobin.
Nadir is defined as the lowest counts (for ANC, WBC, and platelet counts)/concentration (for hemoglobin) that the cells reach after chemotherapy.
Time to nadir is defined as the time from Baseline to the lowest value recorded up to 120 days following the therapeutic dose.
|
From Baseline until Week 25 and follow-up (up to 130 months)
|
Number of Participants Needing Supportive Care at Week 7 and Week 13
Time Frame: Week 7 and Week 13
|
During the administration of unlabeled Anti-B1 antibody and Iodine-131 Anti-B1 antibody, emergency support for anaphylaxis, including epinephrine, diphenhydramine, hydrocortisone, a laryngoscope, and an endotracheal tube, was readily available.
The use of steroids were discouraged unless other measures were ineffective.
|
Week 7 and Week 13
|
Number of Participants Converting to Human Anti-Murine (Mouse) Antibody (HAMA) Positivity at Any Follow-up Visit From HAMA Negativity at Baseline
Time Frame: Baseline; any follow-up visit (up to 72 months)
|
The number of participants who developed human anti-murine (mouse) anibodies (HAMA) after treatment was measured.
|
Baseline; any follow-up visit (up to 72 months)
|
Overall Survival
Time Frame: From Baseline until Week 25 and follow-up (up to 130 months)
|
Overall survival (time to death) is defined from the start of treatment to the date of death from any cause.
|
From Baseline until Week 25 and follow-up (up to 130 months)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 393229/007
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Study Data/Documents
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Study Protocol
Information identifier: 393229/007Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Dataset Specification
Information identifier: 393229/007Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Clinical Study Report
Information identifier: 393229/007Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Individual Participant Data Set
Information identifier: 393229/007Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Informed Consent Form
Information identifier: 393229/007Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Statistical Analysis Plan
Information identifier: 393229/007Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Annotated Case Report Form
Information identifier: 393229/007Information comments: For additional information about this study please refer to the GSK Clinical Study Register
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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