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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 主要终点
- Number of Participants With the Indicated Grade 4 Hematology Toxicities Following Iodine-131 Anti-B1 Antibody
研究概览
简要总结
This is a multicenter study for the long-term follow-up of surviving patients who are expected to complete or who have completed at least two years of follow-up after treatment with Iodine I 131 Tositumomab (BEXXAR) on studies CP-97-011, CP-98-025, CP-99-032, or CP-99-036. All patients will be assessed for survival and disease status, including subsequent therapy for Diffuse Large B-cell Non-Hodgkin's Lymphoma (NHL), and for long-term safety. Additionally laboratory evaluations consisting of a thyroid stimulating hormone (TSH) level and a complete blood cell (CBC) count with a differential and platelet count will be obtained annually. Additionally, patients who remain in long-term response following Iodine I 131 Tositumomab treatment will be followed for response and progression.
详细描述
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.
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
- •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)
排除标准
- •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
研究组 & 干预措施
Single Arm
tositumomab and iodine I-131 tositumomab
干预措施: tositumomab and iodine I-131 tositumomab (Drug)
结局指标
主要结局
Number of Participants With the Indicated Grade 4 Hematology Toxicities Following Iodine-131 Anti-B1 Antibody
时间窗: 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.
次要结局
- 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)(From Baseline until Week 25 and follow-up (up to 130 months))
- Progression-free Survival (PFS)(From Baseline until Week 25 and follow-up (up to 130 months))
- Time to Treatment Failure (TTF)(From Baseline until Week 25 and follow-up (up to 130 months))
- Total Body Residence Time (TBRT)(From Baseline until Week 25 and follow-up (up to 130 months))
- Number of Participants Needing Supportive Care at Week 7 and Week 13(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(Baseline; any follow-up visit (up to 72 months))
- Overall Survival(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)(From Baseline until Week 25 and follow-up (up to 130 months))
- Time to Recovery From the Indicated Hematology Toxicities(From Baseline until Week 25 and follow-up (up to 130 months))
- Nadir for the Indicated Hematology Toxicities(From Baseline until Week 25 and follow-up (up to 130 months))
- Duration of Response and Duration of Confirmed Complete Response(From Baseline until Week 25 and follow-up (up to 130 months))
- Time to Nadir for the Indicated Hematology Toxicities(From Baseline until Week 25 and follow-up (up to 130 months))