A Phase 1, Multicenter, Dose Escalation Study of CAT-8015 in Patient With Relapsed or Refractory Hairy Cell Leukemia (HCL)
试验速览
- 阶段
- 1 期
- 入组人数
- 40
- 试验地点
- 5
- 主要终点
- Estimate the maximum dose that can be safely administered to a patient
研究概览
简要总结
RATIONALE: The CAT-8015 immunotoxin can bind tumor cells and kill them without harming normal cells. This may be an effective treatment for hairy cell leukemia(HCL) that has not responded to chemotherapy, surgery or radiation therapy.
PURPOSE: Phase I dose escalation study to determine the maximum tolerated dose of CAT-8015 immunotoxin in treating patients who have hairy cell leukemia (HCL) that has not responded to treatment.
详细描述
OUTLINE: Patients receive CAT-8015 IV over 30 minutes on days 1, 3, and 5 followed by rest. Treatment repeats every 4 weeks for up to a total of 10 courses in the absence of dose limiting toxicity, complete response or disease progression. Patients are followed at 1, 3, 6,12,15,18, 21, 24 months following the start of the last treatment cycle.
Cohorts of 3-6 patients each will receive escalating doses of recombinant CAT-8015 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose proceeding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, between16 to 25 new patients will be added to the MTD cohort depending on how well the CAT-8015 is tolerated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •DISEASE CHARACTERISTICS:
- •Confirmed diagnosis of hairy cell leukemia
- •Measurable disease
- •At least one of the following indications for treatment:
- •Neutropenia (ANC <1000 cells/µL)
- •Anemia (Hgb <10g/dL)
- •Thrombocytopenia (Plt <100,000/µL)
- •An absolute lymphocyte count of >20,000 cells/µL, or
- •Symptomatic splenomegaly
- •Patient's must have had at least 2 prior systemic therapies. There must have been at least 2 prior courses of purine analog, or 1 if the response to this course lasted <2 years, or if the patient had unacceptable toxicity to purine analog.
- •PATIENT CHARACTERISTICS:
- •Performance status • ECOG 0-2
- •Life expectancy
- •Life expectancy of greater than 6 months, as assessed by the principal investigator
- •Patients with other cancers who meet eligibility criteria and have had less than 5 years of disease free survival will be considered on a case-by-case basis
- •Ability to understand and sign informed consent
- •Female and male patients agree to use an approved method of contraception during the study
排除标准
- •Documented and ongoing central nervous system involvement with their malignant disease (history of CNS involvement is not an exclusion criterion)
- •History of bone marrow transplant
- •Pregnant or breast-feeding females
- •Patients whose plasma contains either a significant level of antibody to CAT-8015 as measured by ELISA, or antibody that neutralizes the binding of CAT-8015 to CD22 as measured by a competition ELISA.
- •HIV positive serology (due to increased risk of severe infection and unknown interaction of CAT-8015 with antiretroviral drugs)
- •Hepatitis B surface antigen positive
- •Uncontrolled, symptomatic, intercurrent illness including but not limited to: infections requiring systemic antibiotics, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements
- •Hepatic function: serum transaminases (either ALT or AST) or bilirubin:
- •≥ Grade 2, unless bilirubin is due to Gilbert's disease
- •Renal function: serum creatinine clearance ≤60mL/min as estimated by Cockroft-Gault formula
- •Hematologic function:
- •The ANC <1000/cmm, or platelet count <50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy)
- •Baseline coagulopathy > grade 3 unless due to anticoagulant therapy
- •A patient will not be excluded because of pancytopenia ≥ Grade 3, or erythropoietin dependence, if it is due to disease, based on the results of bone marrow studies
- •Pulmonary function:
- •Patients with < 50% of predicted forced expiratory volume (FEV1) or <50% of predicted diffusing capacity for carbon monoxide (DLCO), corrected for hemoglobin concentration and alveolar volume. Note: Patients with no prior history of pulmonary illness are not required to have PFTs. FEV1 will be assessed following bronchodilator therapy.
- •Recent prior therapy:
- •Cytotoxic chemotherapy (except stable doses of prednisone), whole body electron beam radiation therapy, interferon, retinoids or other systemic therapy, or investigational therapy of the malignancy for 3 weeks prior to entry into the trial
- •Less than or equal to < 3 months prior monoclonal antibody therapy (i.e. rituximab)
- •Patients who have received or are receiving radiation therapy less than 3 weeks prior to study entry will be not be excluded providing the volume of bone marrow treated is less than 10% and also the patient has measurable disease outside the radiation port
- •Any history of pseudomonas-exotoxin (PE) immunotoxin administration
结局指标
主要结局
Estimate the maximum dose that can be safely administered to a patient
Characterize the toxicity profile of CAT-8015
Study the clinical pharmacology of CAT-8015
Observe anti-tumor activity, if any.
次要结局
- To assess the immunogenic potential of CAT-8015 to induce antibodies
- To investigate the potential of biomarkers to predict any therapeutic or toxic response.