英文药名：Campath(alemtuzumab Injection for intravenous use) 中文药名：阿仑单抗静脉注射剂 生产厂家：Genzyme公司 药品简介 抗白血病药物alemtuzumab（美国商标名：Campath，欧洲商标名：MabCampath）已经获得美国FDA及欧洲联盟批准的批准上市 Campath-1H，又称阿来组抗体（Alemtuzumab），是一种人源性抗CD52单克隆抗体，可特异性识别淋巴细胞表面的CD52抗原。与靶细胞结合后通过补体依赖性细胞溶解（CDC）、抗体依赖性细胞毒性（ADCC）以及诱导细胞凋亡等机制杀伤靶细胞。 Campath（阿仑单抗 alemtuzumab）注射用于静脉注射 最初的美国批准：2001年 警告： CYTOPENIAS，输液反应和感染 查看完整的盒装警告的完整处方信息。 严重的，包括致命的，血细胞减少，输液反应和感染可能发生。 限制剂量为30毫克（单）和90毫克（每周累计）;更高的剂量会增加全血细胞减少的风险。 逐渐升高剂量并在输注期间监测患者。对3或4级输液反应的预防疗法。 治疗肺囊虫肺炎（PCP）和疱疹病毒感染的预防。 最近的主要变化 警告和注意事项：3/2009 作用机制 Campath结合CD52，存在于B和T淋巴细胞表面的抗原，大部分单核细胞，巨噬细胞，NK细胞和粒细胞亚群。 一部分骨髓细胞，包括一些CD34 +细胞，表达不同水平的CD52。 所提出的作用机制是Campath对白血病细胞的细胞介导的抗体依赖性细胞表面结合。 指征和用法 的Campath是可作为单独的药剂，用于治疗B细胞慢性淋巴细胞性白血病（B-CLL）一个CD52定向溶细胞抗体。 用法和管理 经2小时静脉输注。 上升到推荐剂量30毫克/天，每周三次，持续12周。 在给药前用口服抗组胺药和对乙酰氨基酚预先给药。 用量形式和强度 30毫克/1毫升一次性使用小瓶。 禁忌症 无。 警告和注意事项 血细胞减少症： 治疗期间每周一次获得全血计数（CBC）和血小板计数，治疗后CD4计数直至≥200细胞/μL。 自动免疫或严重血液学不良反应终止。 感染： Campath诱导严重和持续的淋巴细胞减少，并增加感染的风险。如果发生严重感染，则停止治疗直至感染消退。 不要给最近接受Campath的病人服用活病毒疫苗。 不良反应 最常见的不良反应（≥10％）：血细胞减少症，输液反应，巨细胞病毒（CMV）和其他感染，恶心，呕吐，腹泻，失眠和。 注：本品基本停产，目前德国仅有小部份货销售，采购者请以在线咨询为准。。. FULL PRESCRIBING INFORMATION WARNING: CYTOPENIAS, INFUSION REACTIONS, and INFECTIONS Cytopenias: Serious, including fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia can occur in patients receiving Campath. Single doses of Campath greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia [see WARNINGS AND PRECAUTIONS (5.1)]. Infusion Reactions: Campath administration can result in serious, including fatal, infusion reactions. Carefully monitor patients during infusions and withhold Campath for Grade 3 or 4 infusion reactions. Gradually escalate Campath to the recommended dose at the initiation of therapy and after interruption of therapy for 7 or more days [see DOSAGE AND ADMINISTRATION (2)andWARNINGS AND PRECAUTIONS (5.2)]. Infections: Serious, including fatal, bacterial, viral, fungal, and protozoan infections can occur in patients receiving Campath. Administer prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and herpes virus infections [seeDOSAGE AND ADMINISTRATION (2.2)and WARNINGS AND PRECAUTIONS (5.3)]. 1 INDICATIONS AND USAGE Campath is indicated as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). 2 DOSAGE AND ADMINISTRATION 2.1 Dosing Schedule and Administration Administer as an IV infusion over 2 hours. Do not administer as intravenous push or bolus. Recommended Dosing Regimen Gradually escalate to the maximum recommended single dose of 30 mg. Escalation is required at initiation of dosing or if dosing is held≥ 7 days during treatment. Escalation to 30 mg ordinarily can be accomplished in 3 - 7 days. Escalation Strategy: Administer 3 mg daily until infusion reactions are ≤ grade 2 [see ADVERSE REACTIONS (6.1)]. Then administer 10 mg daily until infusion reactions are ≤ grade 2. Then administer 30 mg/day three times per week on alternate days (e.g., Mon-Wed-Fri). The total duration of therapy, including dose escalation, is 12 weeks. Single doses of greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia. 2.2 Recommended Concomitant Medications Premedicate with diphenhydramine (50 mg) and acetaminophen (500-1000 mg) 30 minutes prior to first infusion and each dose escalation. Institute appropriate medical management (e.g. steroids, epinephrine, meperidine) for infusion reactions as needed[see BOXED WARNING,WARNINGS AND PRECAUTIONS (5.2) and ADVERSE REACTIONS (6.1)]. Administer trimethoprim/sulfamethoxazole DS twice daily (BID) three times per week (or equivalent) as Pneumocystis jiroveci pneumonia (PCP) prophylaxis. Administer famciclovir 250 mg BID or equivalent as herpetic prophylaxis. Continue PCP and herpes viral prophylaxis for a minimum of 2 months after completion of Campath or until the CD4+ count is≥ 200 cells/µL, whichever occurs later [seeBOXED WARNING and WARNINGS AND PRECAUTIONS (5.3)]. 2.3 Dose Modification Withhold Campath during serious infection or other serious adverse reactions until resolution. Discontinue Campath for autoimmune anemia or autoimmune thrombocytopenia. There are no dose modifications recommended for lymphopenia. Dose Modification for Neutropenia or Thrombocytopenia [see WARNINGS AND PRECAUTIONS (5.1)] * If the delay between dosing is≥ 7 days, initiate therapy at Campath 3 mg and escalate to 10 mg and then to 30 mg as tolerated [see DOSAGE AND ADMINISTRATION (2.1)]. Hematologic Values Dose Modification* ANC < 250/μL and/or platelet count ≤25,000/μL For first occurrence: Withhold Campath therapy. Resume Campath at 30 mg when ANC ≥ 500/μL and platelet count ≥ 50,000/μL. For second occurrence: Withhold Campath therapy. Resume Campath at 10 mg when ANC ≥ 500/μL and platelet count ≥ 50,000/μL. For third occurrence: Discontinue Campath therapy. ≥ 50% decrease from baseline in patients initiating therapy with a baseline ANC ≤ 250/μL and/or a baseline platelet count ≤ 25,000/μL For first occurrence: Withhold Campath therapy. Resume Campath at 30 mg upon return to baseline value(s). For second occurrence: Withhold Campath therapy. Resume Campath at 10 mg upon return to baseline value(s). For third occurrence: Discontinue Campath therapy. 2.4 Preparation and Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. If particulate matter is present or the solution is discolored, the vial should not be used. DO NOT SHAKE VIAL. Use aseptic technique during the preparation and administration of Campath. Withdraw the necessary amount of Campath from the vial into a syringe. To prepare the 3 mg dose, withdraw 0.1 mL into a 1 mL syringe calibrated in increments of 0.01 mL. To prepare the 10 mg dose, withdraw 0.33 mL into a 1 mL syringe calibrated in increments of 0.01 mL. To prepare the 30 mg dose, withdraw 1 mL in either a 1 mL or 3 mL syringe calibrated in 0.1 mL increments. Inject syringe contents into 100 mL sterile 0.9% Sodium Chloride USP or 5% Dextrose in Water USP. Gently invert the bag to mix the solution. Discard syringe. The vial contains no preservatives and is intended for single use only. DISCARD VIAL including any unused portion after withdrawal of dose. Use within 8 hours after dilution. Store diluted Campath at room temperature (15-30°C) or refrigerated (2-8°C). Protect from light. 2.5 Incompatibilities Campath is compatible with polyvinylchloride (PVC) bags and PVC or polyethylene-lined PVC administration sets. Do not add or simultaneously infuse other drug substances through the same intravenous line. 3 DOSAGE FORMS AND STRENGTHS 30 mg/1 mL single use vial 4 CONTRAINDICATIONS None 5 WARNINGS AND PRECAUTIONS 5.1 Cytopenias Severe, including fatal, autoimmune anemia and thrombocytopenia, and prolonged myelosuppression have been reported in patients receiving Campath. In addition, hemolytic anemia, pure red cell aplasia, bone marrow aplasia, and hypoplasia have been reported after treatment with Campath at the recommended dose. Single doses of Campath greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia. Withhold Campath for severe cytopenias (except lymphopenia). Discontinue for autoimmune cytopenias or recurrent/persistent severe cytopenias (except lymphopenia) [see DOSAGE ANDADMINISTRATION (2.3)]. No data exist on the safety of Campath resumption in patients with autoimmune cytopenias or marrow aplasia [see ADVERSE REACTIONS (6.1)]. 5.2 Infusion Reactions Adverse reactions occurring during or shortly after Campath infusion include pyrexia, chills/rigors, nausea, hypotension, urticaria, dyspnea, rash, emesis, and bronchospasm. In clinical trials, the frequency of infusion reactions was highest in the first week of treatment. Monitor for the signs and symptoms listed above and withhold infusion for Grade 3 or 4 infusion reactions [see ADVERSE REACTIONS (6.1)]. The following serious, including fatal, infusion reactions have been identified in post-marketing reports: syncope, pulmonary infiltrates, acute respiratory distress syndrome (ARDS), respiratory arrest, cardiac arrhythmias, myocardial infarction, acute cardiac insufficiency, cardiac arrest, angioedema, and anaphylactoid shock. Initiate Campath according to the recommended dose-escalation scheme [see DOSAGE AND ADMINISTRATION (2)]. Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g., glucocorticoids, epinephrine, meperidine) for infusion reactions as needed [see DOSAGE AND ADMINISTRATION (2.2)]. If therapy is interrupted for 7 or more days, reinstitute Campath with gradual dose escalation [seeDOSAGE AND ADMINISTRATION (2.3) and ADVERSE REACTIONS (6)]. 5.3 Immunosuppression/Infections Campath treatment results in severe and prolonged lymphopenia with a concomitant increased incidence of opportunistic infections [see ADVERSE REACTIONS (6.1)]. Administer PCP and herpes viral prophylaxis during Campath therapy and for a minimum of 2 months after completion of Campath or until the CD4+ count is≥ 200 cells/µL, whichever occurs later [see DOSAGE AND ADMINISTRATION (2.2)]. Prophylaxis does not eliminate these infections. Routinely monitor patients for CMV infection during Campath treatment and for at least 2 months following completion of treatment. Withhold Campath for serious infections and during antiviral treatment for CMV infection or confirmed CMV viremia (defined as polymerase chain reaction (PCR) positive CMV in ≥ 2 consecutive samples obtained 1 week apart) [see ADVERSE REACTIONS (6.1)]. Initiate therapeutic ganciclovir (or equivalent) for CMV infection or confirmed CMV viremia [see DOSAGE AND ADMINISTRATION (2.3)]. Administer only irradiated blood products to avoid transfusion associatedGraft versus Host Disease (TAGVHD), unless emergent circumstances dictate immediate transfusion.1 In patients receiving Campath as initial therapy, recovery of CD4+ counts to≥ 200 cells/µL occurred by 6 months post-treatment; however at 2 months post-treatment, the median was 183 cells/µL. In previously treated patients receiving Campath, the median time to recovery of CD4+ counts to ≥ 200 cells/µL was 2 months; however, full recovery (to baseline) of CD4+ and CD8+ counts may take more than 12 months [seeBOXED WARNINGand ADVERSE REACTIONS (6)]. 5.4 Laboratory Monitoring Obtain complete blood counts (CBC) at weekly intervals during Campath therapy and more frequently if worsening anemia, neutropenia, or thrombocytopenia occurs. Assess CD4+ counts after treatment until recovery to≥ 200 cells/µL [seeWARNINGS AND PRECAUTIONS (5.3) and ADVERSE REACTIONS (6)]. 5.5 Immunization The safety of immunization with live viral vaccines following Campath therapy has not been studied. Do not administer live viral vaccines to patients who have recently received Campath. The ability to generate an immune response to any vaccine following Campath therapy has not been studied. 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Cytopenias [see WARNINGS AND PRECAUTIONS (5.1)] Infusion Reactions[see WARNINGS AND PRECAUTIONS (5.2)] Immunosuppression/Infections [see WARNINGS AND PRECAUTIONS (5.3)] The most common adverse reactions with Campath are: infusion reactions (pyrexia, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), infections (CMV viremia, CMV infection, other infections), gastrointestinal symptoms (nausea, emesis, abdominal pain), and neurological symptoms (insomnia, anxiety). The most common serious adverse reactions are cytopenias, infusion reactions, and immunosuppression/infections. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data below reflect exposure to Campath in 296 patients with CLL of whom 147 were previously untreated and 149 received at least 2 prior chemotherapy regimens. The median duration of exposure was 11.7 weeks for previously untreated patients and 8 weeks for previously treated patients. Lymphopenia: Severe lymphopenia and a rapid and sustained decrease in lymphocyte subsets occurred in previously untreated and previously treated patients following administration of Campath. In previously untreated patients, the median CD4+ was 0 cells/μL at one month after treatment and 238 cells/μL [25-75% interquartile range 115 to 418 cells/μL at 6 months post-treatment[see WARNINGS AND PRECAUTIONS (5.3)]. Neutropenia: In previously untreated patients, the incidence of Grade 3 or 4 neutropenia was 42% with a median time to onset of 31 days and a median duration of 37 days. In previously treated patients, the incidence of Grade 3 or 4 neutropenia was 64% with a median duration of 28 days. Ten percent of previously untreated patients and 17% of previously treated patients received granulocyte colony stimulating factors. Anemia: In previously untreated patients, the incidence of Grade 3 or 4 anemia was 12% with a median time to onset of 31 days and a median duration of 8 days. In previously treated patients, the incidence of Grade 3 or 4 anemia was 38%. Seventeen percent of previously untreated patients and 66% of previously treated patients received either erythropoiesis stimulating agents, transfusions or both. Thrombocytopenia: In previously untreated patients, the incidence of Grade 3 or 4 thrombocytopenia was 14% with a median time to onset of 9 days and a median duration of 14 days. In previously treated patients, the incidence of Grade 3 or 4 thrombocytopenia was 52% with a median duration of 21 days. Autoimmune thrombocytopenia was reported in 2% of previously treated patients with one fatality. Infusion reactions: Infusion reactions, which included pyrexia, chills, hypotension, urticaria, and dyspnea, were common. Grade 3 and 4 pyrexia and/or chills occurred in approximately 10% of previously untreated patients and in approximately 35% of previously treated patients. The occurrence of infusion reactions was greatest during the initial week of treatment and decreased with subsequent doses of Campath. All patients were pretreated with antipyretics and antihistamines; additionally, 43% of previously untreated patients received glucocorticoid pre-treatment. Infections: In the study of previously untreated patients, patients were tested weekly for CMV using a PCR assay from initiation through completion of therapy, and every 2 weeks for the first 2 months following therapy. CMV infection occurred in 16% (23/147) of previously untreated patients; approximately one-third of these infections were serious or life threatening. In studies of previously treated patients in which routine CMV surveillance was not required, CMV infection was documented in 6% (9/149) of patients; nearly all of these infections were serious or life threatening. Other infections were reported in approximately 50% of patients across all studies. Grade 3 - 5 sepsis ranged from 3% to 10% across studies and was higher in previously treated patients. Grade 3 - 4 febrile neutropenia ranged from 5 to 10% across studies and was higher in previously treated patients. Infection-related fatalities occurred in 2% of previously untreated patients and 16% of previously treated patients. There were 198 episodes of other infection in 109 previously untreated patients; 16% were bacterial, 7% were fungal, 4% were other viral, and in 73%, the organism was not identified. Cardiac: Cardiac dysrhythmias occurred in approximately 14% of previously untreated patients. The majority were tachycardias and were temporally associated with infusion; dysrhythmias were Grade 3 or 4 in 1% of patients. Previously Untreated Patients Table 1contains selected adverse reactions observed in 294 patients randomized (1:1) to receive Campath or chlorambucil as first line therapy for B-CLL. Campath was administered at a dose of 30 mg intravenously three times weekly for up to 12 weeks. The median duration of therapy was 11.7 weeks with a median weekly dose of 82 mg (25-75% interquartile range: 69 mg – 90 mg). Table 1 Per Patient Incidence of Selected*Adverse Reactions in Treatment Naive B-CLL Patients Campath (n=147) Chlorambucil (n=147) * Adverse reactions occurring at a higher relative frequency in the Campath arm   NCI CTC version 2.0 for adverse reactions; NCI CTCAE version 3.0 for laboratory values   CMV viremia (without evidence of symptoms) includes both cases of single PCR positive test results and of confirmed CMV viremia (≥ 2 occasions in consecutive samples 1 week apart). For the latter, ganciclovir (or equivalent) was initiated per protocol. All Grades† % Grades 3-4 % All Grades % Grades 3-4 % Blood and Lymphatic System Disorders Lymphopenia 97 97 9 1 Neutropenia 77 42 51 26 Anemia 76 13 54 18 Thrombocytopenia 71 13 70 14 General Disorders and Administration Site Conditions Pyrexia 69 10 11 1 Chills 53 3 1 0 Infections and Infestations CMV viremia‡ 55 4 8 0 CMV infection 16 5 0 0 Other infections 74 21 65 10 Skin and Subcutaneous Tissue Disorders Urticaria 16 2 1 0 Rash 13 1 4 0 Erythema 4 0 1 0 Vascular Disorders Hypotension 16 1 0 0 Hypertension 14 5 2 1 Nervous System Disorders Headache 14 1 8 0 Tremor 3 0 1 0 Respiratory, Thoracic and Mediastinal Disorders Dyspnea 14 4 7 3 Gastrointestinal Disorders Diarrhea 10 1 4 0 Psychiatric Disorders Insomnia 10 0 3 0 Anxiety 8 0 1 0 Cardiac Disorders Tachycardia 10 0 1 0 Previously Treated Patients Additional safety information was obtained from 3 single arm studies of 149 previously treated patients with CLL administered 30 mg Campath intravenously three times weekly for 4 to 12 weeks (median cumulative dose 673 mg [range 2 – 1106 mg]; median duration of therapy 8.0 weeks). Adverse reactions in these studies not listed inTable 1 that occurred at an incidence rate of > 5% were fatigue, nausea, emesis, musculoskeletal pain, anorexia, dysesthesia, mucositis, and bronchospasm. 6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. Using an ELISA assay, anti-human antibodies (HAHA) were detected in 11 of 133 (8.3%) previously untreated patients. In addition, two patients were weakly positive for neutralizing activity. Limited data suggest that the anti-Campath antibodies did not adversely affect tumor response. Four of 211 (1.9%) previously-treated patients were found to have antibodies to Campath following treatment. The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Campath with the incidence of antibodies to other products may be misleading. 6.3 Postmarketing Experience The following adverse reactions were identified during post-approval use of Campath. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Campath exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) reported frequency of the reaction, or (3) strength of causal connection to Campath. Fatal infusion reactions: [see WARNINGS AND PRECAUTIONS (5.2)]. Cardiovascular: congestive heart failure,cardiomyopathy, decreased ejection fraction (some patients had been previously treated with cardiotoxic agents). Immune disorders:Goodpasture’s syndrome, Graves’ disease, aplastic anemia, Guillain Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, serum sickness, fatal transfusion associated Graft versus Host Disease. Infections: Epstein-Barr Virus (EBV) including EBV-associated lymphoproliferative disorder, progressive multifocal leukoencephalopathy (PML), re-activation of latent viruses. Metabolic: tumor lysis syndrome Neurologic:optic neuropathy 7 DRUG INTERACTIONS No formal drug interaction studies have been performed with Campath. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C Animal reproduction studies have not been conducted with Campath. IgG antibodies, such as Campath, can cross the placental barrier. It is not known whether Campath can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Campath should be given to a pregnant woman only if clearly needed. 8.3 Nursing Mothers Excretion of Campath in human breast milk has not been studied; it is not known whether this drug is excreted in human milk. IgG antibodies, such as Campath, can be excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Campath, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the elimination half-life of Campath and the importance of the drug to the mother. 8.4 Pediatric Use Safety and effectiveness have not been established in pediatric patients. 8.5 Geriatric Use Of 147 previously untreated B-CLL patients treated with Campath, 35% were ≥ age 65 and 4% were ≥ age 75. Of 149 previously treated patients with B-CLL, 44% were ≥ 65 years of age and 10% were ≥ 75 years of age. Clinical studies of Campath did not include sufficient number of subjects age 65 and over to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 10 OVERDOSAGE Across all clinical experience, the reported maximum single dose received was 90 mg. Bone marrow aplasia, infections, or severe infusions reactions occurred in patients who received a dose higher than recommended. One patient received an 80 mg dose by IV infusion and experienced acute bronchospasm, cough, and dyspnea, followed by anuria and death. Another patient received two 90 mg doses by IV infusion one day apart during the second week of treatment and experienced a rapid onset of bone marrow aplasia. There is no known specific antidote for Campath overdosage. Treatment consists of drug discontinuation and supportive therapy. 11 DESCRIPTION Campath (alemtuzumab) is a recombinant DNA-derived humanized monoclonal antibody (Campath-1H) directed against the 21-28 kD cell surface glycoprotein, CD52. Campath-1H is an IgG1 kappa antibody with human variable framework and constant regions, and complementarity-determining regions from a murine (rat) monoclonal antibody (Campath-1G). The Campath-1H antibody has an approximate molecular weight of 150 kD. Campath is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin. Neomycin is not detectable in the final product. Campath is a sterile, clear, colorless, isotonic solution (pH 6.8-7.4) for injection. Each single use vial of Campath contains 30 mg alemtuzumab, 8.0 mg sodium chloride, 1.44 mg dibasic sodium phosphate, 0.2 mg potassium chloride, 0.2 mg monobasic potassium phosphate, 0.1 mg polysorbate 80, and 0.0187 mg disodium edetate dihydrate. No preservatives are added. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Campath binds to CD52, an antigen present on the surface of B and T lymphocytes, a majority of monocytes, macrophages, NK cells, and a subpopulation of granulocytes. A proportion of bone marrow cells, including some CD34+ cells, express variable levels of CD52. The proposed mechanism of action is antibody-dependent cellular-mediated lysis following cell surface binding of Campath to the leukemic cells. 12.3 Pharmacokinetics Campath pharmacokinetics were characterized in a study of 30 previously treated B-CLL patients in whom Campath was administered at the recommended dose and schedule. Campath pharmacokinetics displayed nonlinear elimination kinetics. After the last 30 mg dose, the mean volume of distribution at steady-state was 0.18 L/kg (range 0.1 to 0.4 L/kg). Systemic clearance decreased with repeated administration due to decreased receptor-mediated clearance (i.e., loss of CD52 receptors in the periphery). After 12 weeks of dosing, patients exhibited a seven-fold increase in mean AUC. Mean half-life was 11 hours (range 2 to 32 hours) after the first 30 mg dose and was 6 days (range 1 to 14 days) after the last 30 mg dose. Comparisons of AUC in patients ≥ 65 years (n=6) versus patients < 65 years (n=15) suggested that no dose adjustments are necessary for age. Comparisons of AUC in female patients (n=4) versus male patients (n=17) suggested that no dose adjustments are necessary for gender. The pharmacokinetics of Campath in pediatric patients have not been studied. The effects of renal or hepatic impairment on the pharmacokinetics of Campath have not been studied. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term studies in animals have been performed to establish the carcinogenic or mutagenic potential of Campath, or to determine its effects on fertility in males or females. 14 CLINICAL STUDIES 14.1 Previously Untreated B-CLL Patients Campath was eva luated in an open-label, randomized (1:1) active-controlled study in previously untreated patients with B-CLL, Rai Stage I-IV, with evidence of progressive disease requiring therapy. Patients received either Campath 30 mg IV 3 times/week for a maximum of 12 weeks or chlorambucil 40 mg/m2 PO once every 28 days, for a maximum of 12 cycles. Of the 297 patients randomized, the median age was 60 years, 72% were male, 99% were Caucasian, 96% had a WHO performance status 0-1, 23% had maximum lymph node diameter ≥ 5cm, 34% were Rai Stage III/IV, and 8% were treated in the U.S. Patients randomized to receive Campath experienced longer progression free survival (PFS) compared to those randomized to receive chlorambucil (median PFS 14.6 months vs. 11.7 months, respectively). The overall response rates were 83% and 55% (p < 0.0001) and the complete response rates were 24% and 2% (p < 0.0001) for Campath and chlorambucil arms, respectively. The Kaplan-Meier curve for PFS is shown in Figure 1. Figure 1 Progression Free Survival in Previously Untreated B-CLL Patients1 1Log-rank test adjusted for Rai Stage (I-II vs. III-IV). 14.2 Previously Treated B-CLL Patients Campath was eva luated in three multicenter, open-label, single arm studies of 149 patients with B-CLL previously treated with alkylating agents, fludarabine, or other chemotherapies. Patients were treated with the recommended dose of Campath, 30 mg intravenously, three times per week for up to 12 weeks. Partial response rates of 21 to 31% and complete response rates of 0 to 2% were observed. 15 REFERENCES 1 American Association of Blood Banks, America’s Blood Centers, American Red Cross. Circular of Information for the Use of Human Blood and Blood Components. July 2002. 16 HOW SUPPLIED/STORAGE AND HANDLING Campath (alemtuzumab) is supplied in single-use clear glass vials containing 30 mg of alemtuzumab in 1 mL of solution. Each carton contains three Campath vials (NDC 58468-0357-3) or one Campath vial (NDC 58468-0357-1). Store Campath at 2-8°C (36-46°F). Do not freeze. If accidentally frozen, thaw at 2-8°C before administration. Protect from direct sunlight. Campath-FDA批准治疗B细胞性慢性淋巴细胞性白血病新药。(美国Millennium制药) 美一公司的抗白血病新药获FDA批准 2001年5月11日 美国Millennium制药公司于本周一宣布，该公司与Ilex Oncology公司合作研制的抗白血病药物Campath（alemtuzumab）已经获得美国食品和药品管理局（FDA）的批准。 尽管在临床试验中有患者因使用Campath而死亡，但FDA仍批准该药可用于那些烷化剂和氟达拉宾无效的B细胞性慢性淋巴细胞性白血病治疗。 Campath是一种人源性单克隆抗体，主要作用于存在于B和T淋巴细胞上的CD52抗原，从而破坏淋巴细胞。 尽管Campath临床研究中存在30％的死亡率（约半数是治疗相关性死亡，包括血液毒性反应如骨髓增生低下）以及较高的感染率，但是该药总有效率可达到33%，平均有效持续时间为7个月。在2个小规模临床试验中，其有效率分别为21%和29%，平均有效持续时间分别为7和11个月。 在2000年的晚些时候，FDA顾问委员会投票表决，以14票对1票建议加快Campath批准应用，这将允许药物一边在随访研究中搞清未明的问题，一边上市。但是，必须在包装盒上注明应警惕药物的血液毒性、输注反应和治疗相关的感染。 最近该药品已提请欧洲联盟批准以MabCampath的名称在欧盟市场上市，预计在今年下半年可获欧盟的最终批准。 Millennium制药公司称，作为单独用药或联合治疗，Campath正被考虑用于血液肿瘤包括外周和皮肤T细胞淋巴瘤、自体免疫性疾病如多发性硬化的治疗和器官移植排异反应的治疗。 德国Schering AG公司治疗癌症的氟达拉滨新型口服制剂，Fludara Oral(Ⅰ)已在其第一个市场英国上市，用于B细胞慢性淋巴细胞性白血病(CLL)的二线治疗。静脉注射用氟达拉滨是在烷化剂以后治疗B细胞CLL的金标准二线药，如病人不能上医院去接受静脉注射，则(Ⅰ)是有用的。 在此期间，因FDA顾问委员会于去年年底支持Campath(alemtuzumab),Sche-ring公司的CLL专利业务不久将得到进一步扩大。用烷化剂和氟达拉滨治疗无效的病人可用Campath治疗。该药用于CLL的申报文件正在接受EMEA评审。 另外，Schering已获得Climodien(地诺孕素+雌二醇戊酸酯)的荷兰销售许可证。Climodien是治疗绝经后症状的持续性复合激素替代治疗药。预期今年年底前通过相互承认程序也可获得其余欧盟国家的许可证。 减少器官移植排异新技术Campath 2000-9-30 伦敦消息，英国剑桥大学卡恩教授最近透露，他和同事开发出一种可减少器官移植排异的新技术，在３０名患者身上进行试验获得了良好效果。 植入患者体内的新器官会被患者免疫系统认为是“异物”而遭到排异。为了防止这种情况，医生们在手术中经常同时采用多种药物，对患者免疫系统进行抑制。但这些抑制免疫药物通常副作用较大，并有可能增加患者得癌症和脆骨症等疾病的危险。 英国《独立报》２７日报道说，卡恩教授等研究出的新技术，需要在患者手术前向其体内注入一种名为“坎帕斯”（ＣＡＭＰＡＴＨ）的人工合成抗体。该抗体可暂时清除血液中的淋巴细胞，使免疫系统处于失效状态。这使得器官植入患者体内后，不会马上遭到患者免疫系统的排异。免疫系统在一、两个月的逐渐恢复中，会把被移植器官“误认为”是患者体内原有的组成部分。 研究人员用新技术对３０名接受肾脏移植的患者进行试验后发现，新技术能将被移植器官遭排斥的可能性降低约５０％。另外，采用新技术后患者可只服用一种药物，而药剂量只有原来的一半左右。 美國FDA食品藥物管理局 2001年5月批准上市 德國Schering AG公司治療癌症的氟達拉濱新型口服制劑，用于B細胞慢性淋巴細胞性白血病(CLL)的二線治療。靜脈注射用氟達拉濱是在烷化劑以后治療B細胞CLL的金標准二線藥。 ------------------------------------------- 产地国家: 美国 原产地英文商品名: CAMPATH 30MG/ML/VIAL 3VIALS/BOX 原产地英文药品名: ALEMTUZUMAB 中文参考商品译名: 坎帕斯 30毫克/毫升/瓶 3瓶/盒 中文参考药品译名: 阿仑单抗 生产厂家中文参考译名: ILEX PHARMACEUTICALS 生产厂家英文名: ILEX PHARMACEUTICALS