A Phase II Study of Ofatumumab in Combination With High-dose Methylprednisolone in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- IwCLL-WG Defined Complete Response (CR)
研究概览
简要总结
Patients who have relapsed/refractory CLL and require therapy as per iwCLL guidelines will be eligible. Subjects will receive a treatment with ofatumumab and HDMP for three consecutive 4 week cycles. The primary endpoint is to determine the complete response (CR) to therapy and the secondary endpoints will assess the safety and tolerability of the regimen, the impact of the treatment on progression free, treatment free, overall survival, and pharmacokinetics of ofatumumab. Patients will receive allopurinol for tumor-lysis prophylaxis and antimicrobial prophylaxis.
详细描述
Patients who have relapsed/refractory CLL and require therapy as per iwCLL guidelines will be eligible. Subjects will receive a treatment with ofatumumab and HDMP for three consecutive 4 week cycles. The primary endpoint is to determine the complete response (CR) to therapy and the secondary endpoints will assess the safety and tolerability of the regimen, the impact of the treatment on progression free, treatment free, overall survival, and pharmacokinetics of ofatumumab. Cycles 1-3 will be administered without scheduled interruption every 28 days for a total of 12 weeks of therapy. Patients will receive allopurinol for tumor-lysis prophylaxis and antimicrobial prophylaxis. Blood glucose levels will be monitored immediately after HDMP infusion by finger stick glucometry. Two months following completion of treatment a response assessment will occur per iwCLL guidelines. The treatment will be administered as outpatient, and each cycle will be four weeks in duration.
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
- •Previously treated patients with a diagnosis of CLL
- •Previous treatment with any monoclonal antibody or chemotherapy regardless of response as defined by the iwCLL Working Group Guidelines as evidenced by:
- •progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
- •massive (i.e. at least 6cm below the left costal margin) or progressive or symptomatic splenomegaly
- •massive nodes (i.e. at least 10cm in longest diameter) or progressive or symptomatic lymphadenopathy.
- •progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months.
- •autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy (See Section 10.2)
- •Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: unintentional weight loss of 10% or more within the previous 6 months significant fatigue (i.e. ECOG PS 2 or worse, inability to work or perform usual activities), fevers higher than 100.5ºF or 38.0ºC for 2 or more weeks without other evidence of infection, night sweats for more than 1 month without evidence of infection
- •Subjects must be 18 years of age or older, male or female.
- •ECOG performance status of 0-
- •Subjects must be able to give informed consent.
- •Females of child bearing potential(FCBP)† must have a negative serum or urine pregnancy test within 10 - 14 days prior to and again within 24 hours of starting treatment and agree to use a medically accepted contraceptive method for the duration of this study.
排除标准
- •Hepatitis BsAg positive, Hepatitis BcAb positive, and Hepatitis C positive patients.
- •Known HIV positive patients.
- •Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).
- •Screening laboratory values within these ranges: platelets <50 x 109/L, neutrophils <1.0 x 109/L, creatinine >2.0 times upper normal limit,total bilirubin >1.5 times upper normal limit (unless a known history of Gilbert's disease), ALT >2.5 times upper normal limit (unless due to disease involvement of liver), alkaline phosphatase >2.5 times upper normal limit (unless due to disease involvement of the liver or bone marrow)
- •Inability to provide informed consent.
- •Concurrent malignancy (excluding basal and squamous cell skin cancers).
- •Active fungal, bacterial, and/or viral infection.
- •History of peptic ulcer disease resulting in GI bleeding within the last 6 months.
- •Untreated metabolic disorders such as hypothyroidism and Cushing's disease.
- •History of steroid-induced psychosis.
- •Estimated life expectancy of less than 3 months by the investigator's best clinical judgment.
- •Serious medical condition that would render the subject medically unstable.
- •Women who are pregnant or breast-feeding.
- •History of Pancreatitis.
- •History of Diverticulitis.
- •Patients with known hypersensitivity to ofatumumab or known history of anaphylaxis to Rituximab or alemtuzumab.
- •Concurrent use of other anti-cancer agents or treatments.
- •Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
研究组 & 干预措施
Ofatumumab/HDMP
High dose methylprednisolone sodium succinate (HDMP) at 1gm/m2 daily as infusion for 3 consecutive days every cycle.
Ofatumumab 300mg administered Day1 of cycle 1 followed by 12 doses of 1000mg administered.
Each patient may receive 3 cycles of treatment in the absence of progressive disease or significant toxicity.
干预措施: Ofatumumab/HDMP (Drug)
结局指标
主要结局
IwCLL-WG Defined Complete Response (CR)
时间窗: 2 months
Responses were assessed two months after completion of therapy. Criteria for complete remission is assessed with: a bone marrow biopsy and repeat CT scan (abdominal, chest and pelvis if initial was abnormal) to confirm iwCLL-WG defined CR. iwCLL-WG Complete Response is defined as: * Peripheral blood lymphocytes (evaluated by blood and differential count) below 4 x 109/L (4000/L). * Absence of lymphadenopathy (\>1.5 cm)of physical exam; AND * No hepatomegaly and splenomegaly on physical exam; AND * Absence of constitutional symptoms; AND * Normal complete blood count as exhibited by neutrophils ≥ 1,500/μl, platelets \> 100,000/μl, hemoglobin \> 11.0g/dL (non-transfused), and lymphocyte count \< 5,000/μl; AND * Bone marrow aspirate and biopsy must be normocellular for age with \<30% of nucleated cells being lymphocytes. Lymphoid nodules must be absent
次要结局
- IwCLL-WG Defined Overall Response Rate (ORR)(2 months)
- IwCLL-WG Defined Partial Response (PR)(2 months)
- IwCLL-WG Defined Stable Disease (SD)(2 months)
- Progression-free Survival (PFS)(2 years)
- IwCLL-WG Defined Nodular Partial Response (PR)(2 months)
- Treatment-Free Survival(2 years)
- Safety and Tolerability Measured Via Adverse Events(2 years)
- Detectable Minimal Residual Disease (MRD)(2 years)
- IwCLL-WG Defined Progressive Disease (PD)(2 months)
研究者
Januario Castro, M.D.
Principal Investigator
University of California, San Diego