Phase II Trial of Pentostatin, Cyclophosphamide, and Ofatumumab for Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 82
- 试验地点
- 4
- 主要终点
- Arm A: Percentage of Complete Responses
研究概览
简要总结
This phase II trial studies how well giving ofatumumab together with pentostatin and cyclophosphamide works in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. Monoclonal antibodies, such as ofatumumab, can block the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as pentostatin and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ofatumumab together with pentostatin and cyclophosphamide may be a better way to block cancer growth.
详细描述
PRIMARY OBJECTIVES:
I. Arm A: To assess the rate of complete response using pentostatin, cyclophosphamide, and ofatumumab in patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) requiring therapy.
II. Arm B: To assess the treatment-free survival rate at 18 months using pentostatin, cyclophosphamide, and ofatumumab induction therapy followed by ofatumumab consolidation in patients with previously untreated CLL or SLL requiring therapy.
SECONDARY OBJECTIVES:
I. Arm A and Arm B: To assess the rate of overall response in patients with previously untreated CLL or SLL requiring therapy and to determine the proportion of patients who achieve a minimal residual disease (MRD) negative state as assessed by flow cytometry in each arm independently.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Diagnosis of CLL according to the National Cancer Institute (NCI) criteria or SLL according to the World Health Organization (WHO) criteria, including previous documentation of:
- •Biopsy-proven SLL
- •Diagnosis of CLL according to NCI working group criteria as evidenced by all of the following:
- •Peripheral blood lymphocyte count of > 5,000/mm^3 consisting of small to moderate size lymphocytes, with < 55% prolymphocytes
- •Immunophenotyping consistent with CLL defined as:
- •The predominant population of lymphocytes share both B-cell antigens (CD19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)
- •Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression)
- •Note: splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL
- •Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative FISH analysis for t(11;14)(immunoglobulin heavy [IgH]/cyclin D1 [CCND1]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for CCND1 on involved tissue biopsy
- •Patients must be previously untreated and meet at least one of the following indications for chemotherapy:
- •Evidence of progressive marrow failure as manifested by the development of or worsening anemia (=< 11 g/dl) and/or thrombocytopenia (=< 100,000/mm^3) not due to autoimmune disease
- •Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly
- •One or more of the following disease-related symptoms:
- •Weight loss > 10% within the previous 6 months
- •Extreme fatigue attributed to CLL
- •Fevers > 100.5 degree Fahrenheit for 2 weeks without evidence of infection
- •Drenching night sweats without evidence of infection
- •Progressive lymphocytosis due to CLL with an increase of > 50% over a two-month period or an anticipated doubling time of less than six months
- •Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate [EGCG], found in green tea or other herbal treatments) will not be considered "prior treatment"
- •Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient for protocol therapy
- •Serum creatinine =< 1.5 x upper normal levels (UNL)
- •Total bilirubin =< 1.5 x UNL unless due to Gilbert's disease; if total bilirubin is > 1.5 x UNL, a direct bilirubin should be performed and must be < 1.5 mg/dL for Gilbert's to be diagnosed
- •Aspartate aminotransferase (AST) =< 3.0 x UNL and alanine aminotransferase (ALT) =< 3.0 x UNL (unless due to hemolysis or CLL)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0, 1, or 2
- •Willingness to provide blood samples as required
- •Able to adhere to the study visit schedule and other protocol requirements
排除标准
- •Any of the following comorbid conditions:
- •New York Heart Association Class III or IV heart disease
- •Recent myocardial infarction (< 1 month)
- •Uncontrolled infection
- •Infection with the human immunodeficiency virus (HIV/acquired immunodeficiency syndrome [AIDS])
- •Infection with known chronic, active Hepatitis C
- •Positive serology for hepatitis B (HB) defined as a positive test for HB surface antigen (HBsAg); in addition, if negative for HBsAg but HB core antibody (HBcAb) positive (regardless of HBsAb status), a HB deoxyribonucleic acid (DNA) test will be performed and if positive the subject will be excluded
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •Other active primary malignancy requiring treatment or limiting survival to =< 2 years
- •Any radiation therapy =< 4 weeks prior to registration
- •Any major surgery =< 4 weeks prior to registration
- •Current use of corticosteroids; EXCEPTION: low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical conditions; Note: previous use of corticosteroids is allowed
- •Active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment; patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
研究组 & 干预措施
Arm A (PCO, closed to accrual as of 8/23/2011)
Patients receive induction therapy comprising ofatumumab IV on day 1 (days 1-2 of course 1 only), pentostatin IV over 30 minutes on day 1, and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
Arm A (PCO, closed to accrual as of 8/23/2011)
Patients receive induction therapy comprising ofatumumab IV on day 1 (days 1-2 of course 1 only), pentostatin IV over 30 minutes on day 1, and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm A (PCO, closed to accrual as of 8/23/2011)
Patients receive induction therapy comprising ofatumumab IV on day 1 (days 1-2 of course 1 only), pentostatin IV over 30 minutes on day 1, and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Ofatumumab (Biological)
Arm A (PCO, closed to accrual as of 8/23/2011)
Patients receive induction therapy comprising ofatumumab IV on day 1 (days 1-2 of course 1 only), pentostatin IV over 30 minutes on day 1, and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Pentostatin (Drug)
Arm B (PCO with ofatumumab consolidation)
Patients receive induction therapy as in Arm A. Patients then receive consolidation therapy comprising ofatumumab IV on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
Arm B (PCO with ofatumumab consolidation)
Patients receive induction therapy as in Arm A. Patients then receive consolidation therapy comprising ofatumumab IV on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm B (PCO with ofatumumab consolidation)
Patients receive induction therapy as in Arm A. Patients then receive consolidation therapy comprising ofatumumab IV on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Ofatumumab (Biological)
Arm B (PCO with ofatumumab consolidation)
Patients receive induction therapy as in Arm A. Patients then receive consolidation therapy comprising ofatumumab IV on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Pentostatin (Drug)
结局指标
主要结局
Arm A: Percentage of Complete Responses
时间窗: 7 months
In Arm A: PCO, the primary endpoint of this trial is the percentage of complete responses. The NCI Working Group criteria was used to assess response to therapy: A Complete Response (CR) is briefly defines as the absence of lymphadenopathy, no heptomegaly nor splenomegaly, neutrophils greater than 1500/ul, platelets \> 100,000/ul, hemoglobin \>11.0 gm/dl, and peripheral blood lymphocytes \<4000uL.
Arm B: Treatment-free Survival at 18 Months
时间窗: 18 months
The primary endpoint Arm B: PCO+O is treatment-free survival rate at 18 months. An event for treatment-free survival will be defined as initiation of subsequent therapy for CLL or death due to any cause. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for event-free survival at 18 months. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.
次要结局
- Overall Response Rate(14 months)
- Depth of Response After Ofatumumab Consolidation(14 months)
- Treatment-free Survival(up to 5 years from registration)