Retreatment Protocol for BL22 Immunotherapy in Relapsed or Refractory Hairy Cell Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Number of Months to Response to Treatment
研究概览
简要总结
BL22 is a type of protein that scientists have created to interact with certain cancer cells. Experiments have shown that BL22 can bind with cancer cells that have a particular kind of protein (called CD22 ) on their surface, and can kill those cells. CD22 is present on certain types of hairy cell leukemia (HCL) cancer cells, and researchers have been working on treatments that will use BL22 and other related proteins to interact with and kill these kinds of cancer cells. The primary purpose of this study will be to provide access to and treatment with BL22 for patients who have HCL in order to determine their response to the treatment. In addition, the study will assess potential side effects of BL22 and examine why some patients respond better than others to treatment with BL22 and related therapies.
This study will include about 21 to 25 adults who have been diagnosed with forms of HCL that have not responded well to standard treatments such as surgery, chemotherapy, or radiation therapy. These adults also will have received anti-CD22 therapies before, potentially including treatments with BL22, and have not developed immunity or resistance to these treatments.
Prior to the study, patients will undergo a 1- to 2-week screening period to assess their eligibility for treatment. Eligible patients will participate in the study for up to 16 cycles of treatment, with each cycle lasting approximately 4 weeks. For each cycle, patients will receive 1 prescribed dose of BL22 every other day for a total of 3 doses per cycle, and will be assessed after every cycle to evaluate the success of the treatment. During the evaluation visits, patients will be required to have a brief physical examination, give blood and urine samples for testing, and undergo other tests as need to check heart and kidney function and assess the state of the leukemia. Patients who agree will give additional blood, urine, or bone marrow samples for future research purposes.
详细描述
Background:
BL22, also called CAT-3888 or RFB4(dsFv)-PE38, is a recombinant immunotoxin containing an Fv fragment of an anti-CD22 monoclonal antibody and truncated Pseudomonas exotoxin (PE).
In Phase 1 and 2 trials in patients with chemoresistant hairy cell leukemia (HCL), BL22 showed 47-61% complete remission (CR) rates and 12% of HCL patients had a completely reversible hemolytic uremic syndrome (HUS).
A mutant of BL22, termed CAT-8015 or HA22, differs by 3 amino acids and has higher binding affinity to CD22 compared to BL22 (15-fold greater). CAT-8015 is currently undergoing Phase 1 testing in HCL and other diseases.
HCL patients who have previously received recombinant anti-CD22 immunotoxin (BL22, CAT-8015, or LMB-2) may benefit from additional BL22 administration.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BL22 Immunotherapy
30 micrograms/kg intravenous over 30 minutes every other day (QOD) on days 1, 3, 5, of a 4 week cycle (at least 26 days) for a maximum of 16 cycles or until they become ineligible.
干预措施: BL22 (CAT-3888) (Drug)
结局指标
主要结局
Number of Months to Response to Treatment
时间窗: 2/14/2009 till 6/24/2010
Response is defined by the Response Evaluation Criteria in the protocol, namely the earliest point where all relevant tests (i.e. lab tests, physical exam, radiology results) are consistent with complete response (CR) or partial response (PR). CR or PR must be confirmed for at least 4 weeks. Complete response: No evidence of leukemic cells by routine H/E stains of the peripheral blood and bone marrow. Partial response:neutrophils \>/= 1,500/micrograms/L or 50% improvement over baseline without growth factors for at least 4 weeks.
次要结局
- Number of Patients Who Developed Neutralizing Antibodies After One or More Cycles of BL22(24 weeks)
- Number of Patients With ex Vivo Sensitivity Who Respond Clinically(Time to CR can be between 2 months and 1 year)
- Number of Participants With Adverse Events(2 years & 6 months)
- Number of Participants With Complete Response (CR) Who Resolve the Bone Marrow Abnormality by Magnetic Resonance Imaging (MRI)(Bone marrow biopsy and MRI 4 weeks after patients meeting blood criteria for CR, and if CR is present, repeat bone marrow biopsy and MRI every 12 months. Bone marrow biopsy and MRI is not done in patients with PR as best response.)
- Percentage of Patients Who Respond Clinically, Who Also Have Normalization in sCD22 or sCD25(patients may undergo lymphapheresis before the first and/or later cycles up to 12 months after achieving CR or PR)
- Correlation Between Number of Prior Cycles of BL22 With Immunogenicity on This Protocol(Within 2 months of end of treatment ( measure antibodies before each cycle))
- Percentage of Patients Who Make Antibodies(24 weeks)
- Percentage of Patients Who Have Dose Limiting Toxicity (DLT)(24 weeks)
研究者
Robert Kreitman, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)