Multicenter, Pivotal Phase III Study of Iodine-131 Anti-B1 Antibody (Murine) Radioimmunotherapy for Chemotherapy Refractory Low Grade B Cell Lymphomas and Low Grade Lymphomas That Have Transformed to Higher Grade Histologies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 主要终点
- Number of Participants (Par.) Receiving TST and I 131 TST With a Response >=30 Days Versus Par. With a Response >=30 Days After Their Last Qualifying Chemotherapy Regimen (LQCR), Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel
研究概览
简要总结
The results from Phase 1/2 (RIT-I-000) and Phase 2 (RIT-II-001) studies of Tositumomab and Iodine I 131 Tositumomab (TST/I-131 TST) demonstrated that TST/ I-131 TST produced a high response rate in patients with chemotherapy-relapsed/refractory, low-grade or transformed low-grade Non-Hodgkin's Lymphoma (NHL). On the basis of these results this study was designed to compare the efficacy of TST/ I-131 TST to the last qualifying chemotherapy regimen in patients with chemotherapy-refractory, low-grade or transformed low-grade NHL.
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 and female subjects ≥18 years of age with histologically confirmed at initial diagnosis, previously treated (at least 2 prior chemotherapy regimens), low-grade NHL or low-grade lymphoma that had transformed to intermediate- or high-grade histology.
排除标准
- •Subjects 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 intratrebecular space involved exceeds 10% in a unilateral biopsy. The mean of bilateral biopsies must be no more than 25%.
- •Cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks prior to study entry or persistent clinical evidence of toxicity.
- •Prior stem cell transplant.
- •Active obstructive hydronephrosis.
- •Evidence of active infection requiring intravenous (IV) antibiotics at the time of study entry.
- •New York Heart Association Class III or IV heart disease or other serious illness that would preclude evaluation.
- •Prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for 5 years.
- •Known HIV infection.
- •Known brain or leptomeningeal metastases.
- •Subjects who are pregnant or nursing.
- •Previous allergic reactions to iodine. This does not include reactions to intravenous iodine-containing contrast materials.
- •Prior exposure to monoclonal or polyclonal antibodies of any non-human species for either diagnostic or therapeutic purposes, including engineered chimeric and humanized antibodies.
- •Prior radioimmunotherapy.
- •Progressive disease within 1 year of irradiation arising in a field that has been previously irradiated with >3500 cGy.
- •Current use of either approved or non-approved (through another protocol) anti-cancer drugs or biologics
- •De novo intermediate- or high-grade lymphoma.
结局指标
主要结局
Number of Participants (Par.) Receiving TST and I 131 TST With a Response >=30 Days Versus Par. With a Response >=30 Days After Their Last Qualifying Chemotherapy Regimen (LQCR), Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel
时间窗: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Par. with response are those with complete response (CR; complete resolution of all disease-related radiological abnormalities and the disappearance of all signs/symptoms related to disease), complete response unconfirmed (CRu; meets characteristics of CR, except the nodal size hasn't regressed sufficiently, or there is indeterminate bone marrow), or partial response (PR; \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions). Participants' LQCR was used as a comparator for subsequent treatment with Iodine I 131TST.
Duration of Response for Par. Receiving TST and I 131 TST With a Response >=30 Days Versus the Number of Par. With a Response >=30 Days After Their LQCR, as Assessed by the MIRROR Panel
时间窗: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Duration of response is defined as the time from the first documented response (for par. with complete response, complete response unconfirmed, or partial response) until disease progression (DP). DP is defined as a \>=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) 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 centimeters (cm) in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.
次要结局
- Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Overall Survival(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Time to HAMA Positivity From the First Dosimetric Dose(HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With the Indicated Primary Cause of Death(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With the Indicated Time to Death From the Last Dose of Study Drug(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With the Indicated Fatal SAEs Related to Study Drug(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With the Indicated SAEs Related to Study Drug(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Before Receiving the Dosimetric Dose) But Positive or Negative After Receiving the Dosimetric Dose(HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Time to Progression of Disease or Death, as Assessed by the Investigator(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Time to Treatment Failure, as Assessed by the Investigator(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With an Infection for Which Anti-infectives Were Administered(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With the Indicated Type of Infection(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)
- Number of Participants With Hypothyroidism Prior to Therapy and After the Therapeutic Dose(Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months)