Clinical trial NCT00996593: Study of Iodine-131 Anti-B1 Antibody for Patients With Non Hodgkin's Lymphoma Who Have Previously Received Rituximab
Official title: Phase II Study of Iodine-131 Anti-B1 Antibody for Non Hodgkin's Lymphoma Patients Who Have Previously Received Rituximab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Non-Hodgkin
Keywords: Tositumomab
radioimmunotherapy
rituximab
anti-B1
I 131
Bexxar
iodine
non-Hodgkin's lymphoma
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-10-16
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 \<1.5 x upper limit of normal \[ULN\]) and hepatic function (defined as total bilirubin \<1.5 x ULN and aspartate transaminase \[AST\] \<5 x ULN) within 14 days of study entry.
* Patients must have bi-dimensionally measurable disease. At least one lesion must be greater than or equal to 2 x 2 cm (by computed tomography \[CT\] scan).
* Patients must be at least 18 years of age.
* Patients must give written informed consent and sign an IRB/EC- approved informed consent form prior to study entry.

Exclusion Criteria

* Patients with more than an average of 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically within 42 days of study entry. Bilateral posterior iliac crest core biopsies are required if the percentage of intratrabecular space involved exceeds 10% on a unilateral biopsy. The mean of bilateral biopsies must be no more than 25%.
* Patients who received cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks prior to study entry (6 weeks of nitrosourea compounds) or who exhibit persistent clinical evidence of toxicity. The use of systemic steroids must be discontinued at least 1 week prior to study entry.
* Patients with prior hematopoietic stem cell transplant following high-dose chemotherapy or chemo/radiotherapy.
* Patients with active obstructive hydronephrosis.
* Patients with evidence of active infection requiring intravenous (IV) antibiotics at the time of study entry.
* Patients with New York Heart Association class III or IV 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 the patient has been disease-free for 5 years.
* Patients with known HIV infection.
* Patients with known brain or leptomeningeal metastases.
* Patients who are pregnant or nursing. Patients of childbearing potential must undergo a pregnancy test within 7 days of study entry and radiolabeled antibody is not to be administered until a negative result is obtained. Males and females must agree to use effective contraception for 6 months following the radioimmunotherapy.
* Patients with previous allergic reactions to iodine. This does not include reacting to IV iodine-containing contrast materials.
* Patients who previously received radioimmunotherapy.
* Patients with progressive disease within 1 year of irradiation arising in a field that has been previously irradiated with \> 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.

Primary outcomes:
measure: Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Number of Participants With Confirmed Complete Response (CR) as Assessed by the Investigator
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) as Assessed by the Investigator
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Number of Participants With Confirmed Partial Response (PR) as Assessed by the Investigator
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Duration of Response for All Confirmed Responders (CR, CCR, or PR) as Assessed by the Investigator
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Duration of Response for Confirmed CR as Assessed by the Investigator
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Duration of Response for CR and CCR as Assessed by the Investigator
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Duration of Response for All Confirmed Partial Responders as Assessed by the Investigator
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: 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
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Duration of Response for All Participants Classified as Responders With or Without a Prior Response to Rituximab
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: 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
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Duration of Response for All Participants With CR With or Without a Prior Response to Rituximab
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Progression-free Survival for Participants With or Without a Prior Response to Rituximab
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Time to Progression of Disease or Death in All Responders, Participants With CR + CCR, and Participants With PR as Assessed by the Investigator
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Overall Survival
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
Secondary outcomes:
measure: Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Number of Participants With the Indicated Type of Infection
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Number of Participants With an Infection for Which Anti-infectives Were Administered
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Number of Participants With Serious Adverse Events (SAE) Related to Study Drug
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Nadir Values for ANC, a Hematologic Parameter
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Nadir Values for Hemoglobin, a Hematologic Parameter
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Nadir Values for Hematologic Parameters Platelets and WBC Count
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
measure: Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities
timeFrame: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: