Dosimetry/Validation Study of 131Iodine-Anti B1 (Murine) Radioimmunotherapy for Chemotherapy Refractory Low Grade B Cell Lymphomas and Low Grade Lymphomas That Have Transformed to Higher Grade Histologies

Multicenter, Phase II Dosimetry/Validation Study of 131Iodine-Anti B1 (Murine) Radioimmunotherapy for Chemotherapy Refractory Low Grade B Cell Lymphomas and Low Grade Lymphomas That Have Transformed to Higher Grade Histologies

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01224821

Acronym

RIT-II-001

Enrollment

Registered

2010-10-20

Start date

1995-12-31

Completion date

2008-05-31

Last updated

2016-12-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoma, Non-Hodgkin

Keywords

iodine I 131 tositumomab, anti-B1 Antibody, Bexxar, radioimmunotherapy, tositumomab

Brief summary

Study RIT-II-001 is a phase II, multicenter study of the safety, tumor and organ dosimetry, dosimetry methods, and efficacy of Iodine-131 Anti-B1 Antibody for the treatment of patients with low-grade or transformed low-grade non-Hodgkin's lymphoma (NHL). The primary objective of this study is to demonstrate that each site could accurately conduct the whole body dosimetry required for the safe and effective dosing of Iodine-131 Anti-B1 Antibody. Additional objectives of this study are to evaluate the efficacy, dosimetry, and safety of Iodine-131 Anti-B1 Antibody.

Interventions

BIOLOGICALTositumomab (Anti-B1 Antibody) and Iodine-131 Tositumomab

Patients receive a dosimetric dose consisting of 450 milligrams (mg) of unlabeled tositumomab (TST, Anti-B1 Antibody) intravenously (IV) followed by 5 milliCurie (mCi) of Iodine I 131 TST IV. Serial whole body sodium iodide probe scintillation counts and whole body conjugate view gamma camera scans obtained approximately 1 hour after administration and then daily for the next 7 days were used to determine the radioactive clearance and the dose of iodine I 131 TST required to deliver a 75 centigray (cGy) therapeutic dose. The therapeutic dose was administered 7-14 days after the dosimetric dose and consisted of TST 450 mg and an activity of Iodine 131 calculated to deliver 75 cGy or 65 cGy of total body irradiation, depending on platelet count, and 35 mg TST.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Patients must have a histologically confirmed diagnosis of low-grade non-Hodgkin's B-cell lymphoma or low-grade lymphoma that has transformed to intermediate-, or high-grade lymphoma (transformed lymphoma) according to the Working Formulation for Clinical Usage (IWF A, B, and C). * Patients must have evidence that their tumor tissue expresses the CD20 antigen. * Patients must have progressive disease of either low-grade or transformed lymphoma within one year of completion of the last chemotherapy regimen administered. * Patients must have been previously treated with at least one chemotherapy regimen that included an anthracycline or anthracenedione. * Patients must have a performance status of at least 60% on the Karnofsky Scale and anticipated survival of at least three months. * Patients must have an absolute granulocyte count of over 1,500 /mm3 and a platelet count above 100,000 /mm3 within seven days of study entry. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products. * Patients must have normal renal function (creatinine less than 2.0 mg/dL) and hepatic function (bilirubin less than 2.0 mg/dL) within seven days of study entry. * Patients must have bi-dimensionally measurable or evaluable progressive lymphoma disease (at least a 25% increase in tumor size or new sites of disease when compared to the last best disease response). Progression must have occurred within 12 months of the preceding response. * Patients must be at least 18 years of age. * Patients must give written informed consent and sign an approved informed consent form prior to study entry.

Exclusion criteria

* Patients with more than an average of 25% of the intertrabecular marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically at study entry. * Patients who have received cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within FOUR weeks prior to study entry (six weeks for nitrosourea compounds) or who exhibit persistent clinical evidence of toxicity. The use of steroids must have been discontinued (except maintenance-dose steroids) at least one week prior to study entry and patients must then show evidence of stable or progressive disease. * Patients with prior hematologic stem cell transplant following high-dose chemotherapy or chemo/radiotherapy . * Patients with obstructive hydronephrosis. * Patients with evidence of active infection requiring intravenous antibiotics at the time of study entry. * Patients with New York Heart Association class 3 or 4 heart disease or other serious illness that would preclude evaluation. * Patients with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which patient has been disease-free for five years. * Patients with known HIV infection. * Patients with known brain or leptomeningeal metastases. * Patients who are pregnant. Patients of child-bearing potential must undergo a pregnancy test within seven days of study entry. Males and females must agree to use effective contraception during the study. * Patients with previous allergic reactions to iodine. This does not include IV contrast materials. * Patients who were previously given any monoclonal or polyclonal antibodies of any foreign species for either diagnostic or therapeutic purposes. This includes engineered chimeric and humanized antibodies. * Patients who previously received radioimmunotherapy. * Patients with progressive disease in a field that has been previously irradiated with more than 3500 cGy. * Patients who are on another protocol involving non-approved drugs or biologics.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Who Received the Therapeutic Dose at the Seven Clinical Research Sites	Day 1 within one hour of infusion (I) and prior to urination (U); Days 2, 3, and 4 after dosimetric dose (DD) I, following U; Days 6 and 7 after DD I, following U	The dosimetry methods were validated for seven different clinical research sites.

Secondary

Measure	Time frame	Description
Number of Participants (Par.) With Response (CR, CCR, or PR), as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Par. with response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).
Number of Participants With Confirmed Response (CR, CCR, or PR), as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).
Number of Participants With CR and CCR, as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	The total number of participants with CR and CCR was reported. CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Clinical Complete Response: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present.
Number of Participants With Confirmed CR and CCR, as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	The total number of participants with CR and CCR was reported. Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Clinical Complete Response: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present.
Duration of Response for All Confirmed Responders (CR, CCR, or PR), as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Duration of response is defined as the time from the first documented response until disease progression. Disease progression is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.
Duration of Response for All Unconfirmed Responders (CR, CCR, or PR), as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Duration of response is defined as the time from the first documented response until disease progression. Disease progression is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.
Duration of Response for All Confirmed Complete Responders, as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Duration of response is defined as the time from the first documented response until disease progression. Disease progression is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.
Number of Participants With the Indicated Therapeutic Doses (TD) (Total Body Dose)	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Based on their platelet count and body weight. Participants received different TDs of TST. For obese participants (weighing more than 137% of their calculated lean body weight), the calculation to determine the administered activity (mCi) was performed using the maximum effective mass (i.e., the minimum of the participant's mass and 137% of their calculated lean body weight). The administered activity (mCi) for participants with a Baseline platelet count of 100001-149999 cells/millimeter cubed (mm\^3) was reduced to a 65 cGy total body dose, after any adjustment for obesity.
Duration of Response for All Confirmed Clinical Complete Responders, as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Duration of response is defined as the time from the first documented response until disease progression. Disease progression is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.
Duration of Response for All Unconfirmed Clinical Complete Responders, as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Duration of response is defined as the time from the first documented response until disease progression. Disease progression is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.
Median Time to Treatment Failure for All Participants	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Time to treatment failure is defined as the length of time from the date of enrollment to the first incidence of treatment withdrawal, study removal, progression, and/or alternative therapy for the participant's lymphoma, or death.
Overall Survival	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Overall survival is defined as the time from the treatment start date to the date of death from any cause. Time to death is the time from the dosimetric dose to the date of death.
Time to Disease Progression or Death for Responders, as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Progression-free survival or time to progression is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death.
Time to Disease Progression or Death for All Participants, as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Progression-free survival or time to progression is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death.
Duration of Response for All Unconfirmed Complete Responders, as Assessed by the Investigator	Participants were evaluated for up to 142 months in Study 104731 or were followed in the long-term follow-up study (Study 104526) for up to 136.3 months	Duration of response is defined as the time from the first documented response until disease progression. Disease progression is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.

Participant flow

Pre-assignment details

Participants (par.) received radioimmunotherapy of tositumomab (TST) and Iodine I 131 TST in 2 phases (Ph.): Ph. 1, dosimetric dose; Ph. 2, therapeutic dose. Par. were evaluated until disease progression, they died, or they were on study for 2 years. Par. completing 2 years of study could enter a long-term follow-up study (BEX104526; NCT00240591).

Participants by arm

Arm	Count
TST and Iodine I 131 TST Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of unlabeled tositumomab (TST) intravenously (IV) followed by 5 milliCurie (mCi) of Iodine I 131 TST IV. Serial whole body sodium iodide probe scintillation counts and whole body conjugate view gamma camera scans obtained approximately 1 hour after DD administration and then daily for the next 7 days were used to determine the radioactive clearance (RC) and the dose of iodine I 131 TST required to deliver a 75 centigray (cGy) therapeutic dose (TD). The TD was administered 7-14 days after the DD and consisted of TST 450 mg and an activity of Iodine 131 calculated to deliver 75 cGy or 65 cGy of total body irradiation, depending on platelet count, and 35 mg TST. Participants who had completed at least 6 months of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in Study BEX104526 were followed for up to 10 years.	47
Total	47

Arm

Count

TST and Iodine I 131 TST

Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of unlabeled tositumomab (TST) intravenously (IV) followed by 5 milliCurie (mCi) of Iodine I 131 TST IV. Serial whole body sodium iodide probe scintillation counts and whole body conjugate view gamma camera scans obtained approximately 1 hour after DD administration and then daily for the next 7 days were used to determine the radioactive clearance (RC) and the dose of iodine I 131 TST required to deliver a 75 centigray (cGy) therapeutic dose (TD). The TD was administered 7-14 days after the DD and consisted of TST 450 mg and an activity of Iodine 131 calculated to deliver 75 cGy or 65 cGy of total body irradiation, depending on platelet count, and 35 mg TST. Participants who had completed at least 6 months of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in Study BEX104526 were followed for up to 10 years.

Total

Withdrawals & dropouts

Period	Reason	FG000
Dosimetric and Therapeutic Treatment	Adverse Event	1
Dosimetric and Therapeutic Treatment	Continued Follow-up in Study BEX104526	3
Dosimetric and Therapeutic Treatment	Lost to Follow-up	2
Dosimetric and Therapeutic Treatment	Progressive Disease	38
Dosimetric and Therapeutic Treatment	Started Other Treatment	1
Dosimetric and Therapeutic Treatment	Withdrawal by Subject	1
Long-Term Follow-Up	Completion of 10 Year Follow-up	9
Long-Term Follow-Up	Death	2

Baseline characteristics

Characteristic	TST and Iodine I 131 TST
Age, Continuous	50.6 Years STANDARD_DEVIATION 12
Gender Female	22 Participants
Gender Male	25 Participants
Race/Ethnicity, Customized Asian	1 participants
Race/Ethnicity, Customized Black	1 participants
Race/Ethnicity, Customized White	45 participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	46 / 47
serious Total, serious adverse events	23 / 47

Outcome results

Primary

Number of Participants Who Received the Therapeutic Dose at the Seven Clinical Research Sites

The dosimetry methods were validated for seven different clinical research sites.

Time frame: Day 1 within one hour of infusion (I) and prior to urination (U); Days 2, 3, and 4 after dosimetric dose (DD) I, following U; Days 6 and 7 after DD I, following U

Population: Intent-to-Treat (ITT) Exposed Population: all participants who enrolled in the study and received at least one dose of study drug. One participant did not receive the therapeutic dose.

Arm	Measure	Group	Value (NUMBER)
TST and Iodine I 131 TST	Number of Participants Who Received the Therapeutic Dose at the Seven Clinical Research Sites	Clinical site 003	7 participants
TST and Iodine I 131 TST	Number of Participants Who Received the Therapeutic Dose at the Seven Clinical Research Sites	Clinical site 004	8 participants
TST and Iodine I 131 TST	Number of Participants Who Received the Therapeutic Dose at the Seven Clinical Research Sites	Clinical site 005	8 participants
TST and Iodine I 131 TST	Number of Participants Who Received the Therapeutic Dose at the Seven Clinical Research Sites	Clinical site 006	5 participants
TST and Iodine I 131 TST	Number of Participants Who Received the Therapeutic Dose at the Seven Clinical Research Sites	Clinical site 007	6 participants
TST and Iodine I 131 TST	Number of Participants Who Received the Therapeutic Dose at the Seven Clinical Research Sites	Clinical site 008	6 participants
TST and Iodine I 131 TST	Number of Participants Who Received the Therapeutic Dose at the Seven Clinical Research Sites	Clinical site 009	6 participants

Secondary

Duration of Response for All Confirmed Clinical Complete Responders, as Assessed by the Investigator

Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Duration of response is defined as the time from the first documented response until disease progression. Disease progression is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.