Phase II Trial of Iodine-131 Anti-B1 Antibody for Previously Untreated, Advanced Stage, Low Grade Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 77
- 主要终点
- Number of Participants With Confirmed Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR)
研究概览
简要总结
This is a single-arm, single-institution, phase II study of Iodine-131 Anti-B1 Antibody for patients with previously untreated, advanced-stage (stage III or IV) low-grade non-Hodgkin's B-cell lymphoma. A total of 75-80 patients will be enrolled.
Patients will undergo two phases of the study. In the first phase, termed the "dosimetric dose", patients will receive an infusion of unlabeled Anti-B1 Antibody (450 mg) over 70 minutes (including a 10-minute flush) immediately followed by a 30-minute infusion (including a 10-minute flush) of Anti-B1 Antibody (35 mg) which has been trace-labeled with 5 mCi of Iodine-131. Whole body gamma camera scans will be obtained 5 to 8 times between Days 0 and 7 following the dosimetric dose. Using the dosimetric data from 3 imaging timepoints (the imaging timepoints to be used in decreasing order of preference depending on availability of data are Days 0, 3, and 7; Days 0, 4, and 7; Days 0, 3 and 6; Days 0, 4, and 6; Days 0, 2, and 7; and Days 0, 2, and 6), a patient-specific dose of Iodine- 131 to deliver the desired total body dose of radiotherapy will be calculated. In the second phase, termed the "therapeutic dose", patients will receive a 70-minute infusion (including a 10-minute flush) of unlabeled Anti-B1 Antibody (450 mg) immediately followed by a 30-minute infusion (including a 10-minute flush) of Anti-B1 Antibody (35 mg) labeled with the patient-specific dose of Iodine-131 to deliver a whole body dose of 75 cGy. Patients who are obese will be dosed based upon 137% of their calculated 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 primary endpoint of the study is the determination of the response rate with Iodine-131 Anti-B1 Antibody in previously untreated patients with low-grade non-Hodgkin's lymphoma (NHL). The secondary endpoints include duration of response, safety, radiation dosimetry, and the predictive value of detection of the presence or absence minimal residual disease by molecular techniques on response duration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have a histologically confirmed diagnosis of lowgrade non-Hodgkin's B-cell lymphoma. The following low-grade histologies are included: small lymphocytic (with or without plasmacytoid differentiation); follicular, small cleaved; follicular, mixed small cleaved and follicular large cell (less than 50% large cell component); and monocytoid B-cell lymphoma.
- •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 (Coulter Clone®) or similar commercially available CD20 antibody (>50% of tumor cells are positive) or evidence of CD20 positivity by flow cytometry (>50% of tumor cells are positive) are acceptable evidence of CD20 positivity. Testing of tumor tissue from any time in the course of the patient's disease is acceptable.
- •Patients must have Ann Arbor stage III or IV extent of disease after complete staging.
- •Patients must not have had any previous treatment for low-grade lymphoma including chemotherapy or radiation. They may be newly diagnosed or observed without treatment after diagnosis. Symptomatic and asymptomatic patients will be eligible.
- •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 neutrophil count (ANC) >1500 cells/mm3 and a platelet count >100,000 cells/mm3 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 ≥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- approved informed consent form prior to study entry.
排除标准
- •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 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 active obstructive hydronephrosis.
- •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 were previously given any monoclonal or polyclonal antibodies of any non-human species for either diagnostic or therapeutic purposes. This includes engineered chimeric and humanized antibodies.
- •Patients who are concurrently receiving either approved or nonapproved (through another protocol) anti-cancer drugs or biologics.
研究组 & 干预措施
open-label, single arm
Tositumomab and Iodine I 131 Tositumomab
干预措施: Tositumomab and Iodine I 131 Tositumomab (Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody) (Biological)
结局指标
主要结局
Number of Participants With Confirmed Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR)
时间窗: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Confirmed response required CR, CCR, or PR, which were confirmed by 2 separate response evaluations \>=4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Number of Participants With Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), or Partial Response (PR)
时间窗: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR)
时间窗: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Responses were confirmed by two separate response evaluations at least 4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR)
时间窗: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
次要结局
- Overall Survival(From Study Day 0 (start of treatment) up to 12 years (long-term follow up))
- The Estimated Value Represents the Percentage of Participants With a PR(From Study Day 0 (start of treatment) up to 12 years (long-term follow up))
- Time to Progression of Disease or Death (Progression-free Survival)(From Study Day 0 (start of treatment) up to 12 years (long-term follow up))
- Number of Participants With Resolution of All Baseline B-symptoms by the End of the Study(Baseline and up to 12 years (long-term follow up))
- Number of Participants Who Were Polymerase Chain Reaction (PCR)-Positive at Baseline With Bone Marrow Conversion to a Status of PCR Positive and Negative Any Time After Treatment(Baseline and up to 12 years (long-term follow up))
- Duration of Response (the Time From the First Documented Response to the First Documented Progression) for Participants Who Were PCR Positive at Baseline and Converted to PCR Negative Status After Treatment(Baseline and up to 12 years (long-term follow up))
- Maximum Concentration (Cmax) Values(0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7))
- Progression-free Survival (PFS) Based on Participants' Baseline PCR Status(Baseline and up to 12 years (long-term follow up))
- Initial Half-life (t1/2alpha)(0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7))
- Terminal Half-life (t1/2beta)(0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7))
- Area Under the Curve (AUC) at 0 to 120 Hours and 0 to Infinity Hours(0-120 hours and 0-infinity hours from the dosimetric dose (given only on Day 0) and 0-120 hours and 0-infinity hours from the therapeutic dose (given only on Day 7))
- Clearance Values(0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7))
- Volume of Distribution at Infusion Time 0 (Vd0) and Steady State (Vdss)(0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7))
- Total Body Effective Half-life (EHL)(0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7))
- Normal Organ Dosimetry for the Indicated Organs(0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7))
- Number of Participants With the Indicated Fatal Serious Adverse Events (SAE)(From Baseline up to 12 years from the start of treatment (long-term follow up))
- Number of Participants Evaluable and Not Evaluable for Human Anti-Murine Antibodies (HAMA)(From Baseline up to 2 years from the start of treatment)
- Number of Participants With Conversion to HAMA Positivity Any Time During the Study From Baseline(From Baseline up to 2 years from the start of treatment)
- Time to HAMA Positivity From the First Dosimetric Dose(From Baseline up to 2 years from the start of treatment)
- Number of Participants With Elevated, Low, and Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline(Baseline)
- Participants With Elevated TSH Levels at Baseline With Post Baseline TSH Levels of Low/Normal and Elevated(Baseline and up to 12 years (long-term follow up))
- Time to Elevated TSH Post Baseline for Participants Who Had Low or Normal TSH Levels at Baseline and Elevated Levels Post Baseline(Baseline and up to 12 years from the start of treatment)
- Number of Participants With the Adverse Event (AEs) of Hypothyroidism(Baseline and up to 12 years from the start of treatment)
- Number of Participants With Low or Normal Baseline TSH Levels That Developed Hypothyroidism(Baseline and up to 12 years from the start of treatment)
- Number of Participants Who Received Thyroid Medication After Treatment(From Study Day 0 (start of treatment) up to 12 years (long-term follow up))