Phase II Multicenter Study of Cyclophosphamide, Vincristine, and Prednisone (CVP) Followed by Iodine-131 Anti-B1 Antibody for Patients With Untreated Low-grade Non-Hodgkin's Lymphoma (NHL).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 主要终点
- Number of Participants (Par.) With Unconfirmed Response (Complete Response, Complete Response/Unconfirmed, or Partial Response), as Assessed by the Investigator
研究概览
简要总结
This is a phase II, open-label, multicenter study of the efficacy and safety of sequential administration of CVP x 6 followed by tositumomab and iodine I 131 tositumomab (formerly referred to as tositumomab and iodine I 131 tositumomab). All patients who complete three cycles of CVP, regardless of response, will be eligible for treatment with tositumomab and iodine I 131 tositumomab. Subjects who have rapidly progressive disease prior to completing three cycles of CVP may be removed from study.
In order to proceed to tositumomab and iodine I 131 tositumomab therapy, patients must have completed six cycles of CVP within 20 weeks as described. Patients may proceed to Iodine-131 Anti-B1 Antibody if they have progressive disease documented at the response evaluation following 6 cycles of CVP. In addition, patients must still meet the eligibility inclusion exclusion criteria based upon the week 20 assessments, as applicable. Patients must also have an average of ≤25% bone marrow involved by NHL to receive treatment with tositumomab and iodine I 131 tositumomab. The dosimetric dose of tositumomab and iodine I 131 tositumomab must be given within 28 days of the response evaluation following CVP and no later than 56 days from the first day of the sixth cycle of CVP.
详细描述
This is a phase II, open-label, multicenter study of the efficacy and safety sequential administration of cycolophosphamide, vacristine, and prednisone (CVP) x6 cycles followed by tositumomab and iodine I 131 tositumomab for previously untreated subjects with low-grade Non-Hodgkin's Lymphoma (NHL). CVP will be repeated every 21 days for a total of six cycles. tositumomab and iodine I 131 tositumomab will begin within 56 days following the first day of the sixth cycle of CVP. Subjects will undergo two dosing phase for the tositumomab and iodine I 131 tositumomab therapy. In the first phase, "dosimetric dose", patients will receive an infusion of unlabeled Anti-B1 Antibody (450mg) over 60 minutes followed by a 30 minute infusion (including a 10-minutes flush) of Anti-B1 (35mg) containing 5mCi 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 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 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 the subjects -specific dose of Iodine-131 calculate to deliver a 75cGy total body radiation dose. Subjects who have platelet counts of 100,000-149,999 cells/mm3 will receive 65 cGy; obese patients will be dosed base upon 137% of their lean body mass. Subjects 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 tositumomab and iodine I 131 tositumomab (i.e., the dosimetric dose) and continuing for 14 days following the least infusion of tositumomab and iodine I 131 tositumomab (i.e., the therapeutic dose).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Subjects must have a histologically confirmed initial diagnosis of low-grade non-Hodgkin's B-cell lymphoma according to the International Working Formulation (IWF) (32) (i.e., small lymphocytic with or without plasmacytoid differentiation; follicular small cleaved cell; or follicular, mixed small cleaved and large cell).
- •Subjects must have Ann Arbor Stage III, Stage IV, or bulky Stage II disease at diagnosis. Bulky Stage II is defined as a mediastinal mass greater than one-third of the maximum chest diameter, or any other mass greater than or equal to 10 cm in maximum diameter.
- •Subjects 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 or evidence of CD20 positivity by flow cytometry are acceptable evidence of CD20 positivity. Testing of tumor tissue from any time in the course of the patient's disease is acceptable.
- •Subjects must have a performance status of at least 60% on the Karnofsky Performance Scale and an anticipated survival of at least 3 months.
- •Subjects must have an ANC≥1500 cells/mm3 and a platelet count ≥100,000 cells/mm3 within 14 days of study enrollment. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products.
- •Subjects must have adequate renal function (defined as serum creatinine <1.5 times the upper limit of normal) and hepatic function (defined as total bilirubin <1.5 times the upper limit of normal and AST <5 times the upper limit of normal) within 14 days of study enrollment.
- •Subjects must have bi-dimensionally measurable disease. At least one lesion must be ≥2.0x2.0 cm by computerized tomography scan.
- •Subjects must be at least 18 years of age.
- •Subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
- •Subjects must give written informed consent and sign an IRB-approved informed consent form prior to study enrollment.
排除标准
- •Subjects who have received prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for their NHL.
- •Subjects with active obstructive hydronephrosis.
- •Subjects with New York Heart Association class III or IV heart disease or other serious illness that would preclude evaluation.
- •Subjects 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 who have been disease-free of another cancer for greater than 5 years must be carefully assessed at the time of study entry to rule out recurrent disease.
- •Subjects with known HIV infection.
- •Subjects who are HAMA positive.
- •Subjects with known brain or leptomeningeal metastases.
- •Subjects who are pregnant or breastfeeding. Males and females must agree to use a contraceptive method from enrollment to 6 months after receiving Iodine 131 Anti B1 Antibody.
- •Subjects with active infection requiring IV anti-infectives at the time of study enrollment.
- •Subjects with intermediate- or high-grade NHL.
结局指标
主要结局
Number of Participants (Par.) With Unconfirmed Response (Complete Response, Complete Response/Unconfirmed, or Partial Response), as Assessed by the Investigator
时间窗: Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.
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), Complete Response/unconfirmed (CRu: complete resolution of all disease-related symptoms; residual lymph node mass \>1.5 centimeters in the greatest transverse diameter that has regressed by \>75%, indeterminate bone marrow, 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 (Par.) With Confirmed Response (Complete Response [CR], Complete Response/Unconfirmed [CRu], or Partial Response [PR]), as Assessed by the Investigator
时间窗: Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.
CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. CRu: complete resolution of all disease-related symptoms; residual lymph node mass \>1.5 centimeters in the greatest transverse diameter that has regressed by \>75%, indeterminate bone marrow, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions. Confirmed response required CR, CRu, or PR, which were confirmed by 2 separate response evaluations \>=4 weeks apart.
次要结局
- Time to Progression of Disease or Death, as Assessed by the Investigator(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)
- DOR for Unconfirmed and Confirmed Complete Response, as Assessed by the Investigator(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)
- Time to Treatment Failure, as Assessed by the Investigator(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)
- Time to Nadir for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, Platelets, and White Blood Cell (WBC) Count(Up to 120 days following the therapeutic dose (given on Study Day 7, following the dosimetric dose) (or the dosimetric dose for participants who did not receive the therapeutic dose))
- Nadir Values for Platelet Count(Up to 120 days following the therapeutic dose (given on Study Day 7, following the dosimetric dose) (or the dosimetric dose for participants who did not receive the therapeutic dose))
- Nadir Values for WBC Count(Up to 120 days following the therapeutic dose (given on Study Day 7, following the dosimetric dose) (or the dosimetric dose for participants who did not receive the therapeutic dose))
- Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs)(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)
- Number of Participants With Unconfirmed Complete Response (CR), as Assessed by the Investigator(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)
- Total Body Residence Time (TBRT; Average Amount of Time TST Spends in the Body, Calculated From the Rate of TB Clearance of Radioactivity During the Dosimetric Dose [DD]) of Iodine 131 TST Antibody Following the DD(Day (D) 0; D 2, 3, or 4; and D 6 or 7)
- Time to Recovery (TTR) to Baseline (BL) for Hematologic Laboratory (Lab.) Evaluations(Up to 120 days following the therapeutic dose (given on Study Day 7, following the dosimetric dose) (or the dosimetric dose for participants who did not receive the therapeutic dose))
- Nadir Values for Absolute Neutrophil Count (ANC)(Up to 120 days following the therapeutic dose (given on Study Day 7, following the dosimetric dose) (or the dosimetric dose for participants who did not receive the therapeutic dose))
- Nadir Values for Hemoglobin(Up to 120 days following the therapeutic dose (given on Study Day 7, following the dosimetric dose) (or the dosimetric dose for participants who did not receive the therapeutic dose))
- Number of Participants With Confirmed Complete Response (CR), as Assessed by the Investigator(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)
- Duration of Response (DOR), as Assessed by the Investigator(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)
- Number of Participants With Any Treatment-related Serious Adverse Event (SAE)(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)
- Number of Participants Who Received Any Supportive Care(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)
- Number of Participants With the Indicated Primary Cause of Death(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)
- Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Study Entry) But Positive or Negative at Month 24(Day 1 to Day 730 (24 months) after receiving the dosimetric dose)
- Overall Survival(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)
- Number of Participants With the Indicated Grade 3 or Grade 4 AEs Possibly or Probably Related to Study Drug(Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.)