Phase II Study of Iodine 131 Anti B1 Antibody for 1st or 2nd Relapsed Indolent B-Cell Lymphomas or B-Cell Lymphomas That Have Transformed to a More Aggressive Histology
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 主要终点
- Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) as Assessed by the Investigator
研究概览
简要总结
This is a single-arm, open-label study of Iodine 131 Anti B1 Antibody for the treatment of 1st or 2nd relapsed indolent B cell lymphomas or B cell lymphomas that have transformed to a more aggressive histology. The primary endpoint of the study is to determine the response rate. Secondary endpoints of the study is to determine the duration of response, time to progression, time-to-treatment failure, safety, and survival.
Forty patients will receive therapy on this study at the 2 clinical sites. Patients will undergo 2 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 on 1) Day 0; 2) Day 2, 3, or 4; and 3) Day 6 or 7 following the dosimetric dose. Using the dosimetric data from the 3 imaging timepoints, a patient-specific dose of Iodine 131 Anti B1 Antibody to deliver the desired total body dose of radiotherapy will be calculated. In the second phase, termed the "radioimmunotherapeutic 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 35 mg Anti B1 Antibody labeled with the 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 (see Appendix A). 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 and continuing for 14 days following the last infusion of Iodine 131 Anti B1 Antibody (i.e., therapeutic dose).
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 B-cell CLL/PLL/SLL; lymphoplasmacytic - immunocytoma; follicle center, follicular, grade I; or follicle center, follicular, grade II NHLs or one of these B-cell lymphomas which has transformed to a more aggressive histology (37).
- •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 (>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 received 1 or 2 prior chemotherapy regimens and have progressed following their last regimen. Patients who have received >2 prior chemotherapy regimens are excluded. Prior therapy with radiation, immunosuppressants, or steroids are not counted as chemotherapy regimens.
- •Patients must have a performance status of at least 60% on the Karnofsky Scale (see Appendix B) and an anticipated survival of at least 3 months.
- •Patients must have an absolute granulocyte count >1,500 x 109/l and a platelet count >100,000 x 109/l 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 upper limit of normal) and hepatic function (defined as total bilirubin <1.5 upper limit of normal and hepatic transaminases [AST + ALT] <5 x upper limit of normal) within 14 days of study entry.
- •Patients must have bi-dimensionally measurable disease. At least one lesion must be >/=2cm x 2 cm (by CT scan).
- •Patients must be at least 18 years of age.
- •Patients must give written informed consent and sign an EC-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%. The procedure for bilateral bone marrow biopsy analysis of marrow involvement is included in Appendix C.
- •Patients who have received cytotoxic chemotherapy, radiation therapy, or cytokine treatment within 4 weeks prior to study entry (6 weeks for nitrosourea compounds) or who exhibit persistent clinical evidence of toxicity. The use of systemic steroids must be discontinued one 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 IV antibiotics at the time of study entry.
- •Patients with New York Heart Association class III or IV heart disease (see Appendix D) 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 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.
- •Patients with known HIV infection.
- •Patients with known brain or leptomeningeal metastases.
- •Patients who are pregnant or breast-feeding. Patients of child-bearing potential must undergo a serum pregnancy test within 7 days prior to 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 treatment.
- •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 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 concurrently receiving either approved or non-approved (through another protocol) anti-cancer drugs or biologics.
- •Patients who have received more than 2 prior chemotherapy regimens. Prior therapy with radiation, immunosuppressants, or steroids are not counted as chemotherapy regimens.
结局指标
主要结局
Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) as Assessed by the Investigator
时间窗: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.
Responses had to be confirmed by 2 separate evaluations occurring \>4 weeks apart. CCR is defined as the complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion =\<2 centimeters (cm) in diameter by radiographic evaluation or =\<1 cm in diameter by physical examination can be considered scar tissue. The extent of disease (EOD) must be unchanged or decreased upon follow-up evaluations. If the EOD was unchanged or if further decreases occurred for \>=6 months, the participant was reclassified as having a CR.
Number of Participants With Confirmed Partial Response (PR) as Assessed by the Investigator
时间窗: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.
Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Confirmed PR is defined as a \>=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) as Assessed by the Investigator
时间窗: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.
Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. CR is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.
Number of Participants With Confirmed Response as Assessed by the Investigator
时间窗: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.
Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed 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), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, 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 Response as Assessed by the Investigator
时间窗: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 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), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, 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).
次要结局
- Duration of Response for All Confirmed Responders (CR, CCR, or PR) as Assessed by the Investigator(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Time to Treatment Failure as Assessed by the Investigator(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Overall Survival(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Number of Participants Who Became Positive or Negative for Human Anti-murine Antibody (HAMA) After Study Treatment(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Time to Progression of Disease or Death as Assessed by the Investigator(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Number of Participants in the Indicated Categories of Thyroid Function Assessment(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Number of Participants With the Indicated Type of Infection(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Number of Participants With an Infection for Which Anti-infectives Were Administered(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Nadir Values for Hematologic Parameters ANC, Platelets, and WBC Count(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Number of Days Each Participant Took to Reach Hypothyroidism After the First Dosimetric Dose(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Nadir Values for Hemoglobin, a Hematologic Parameter(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)
- Time to HAMA Positivity From First Dosimetric Dose(Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528.)