Phase I/II Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-Intensity Chemotherapy in Patients With Acute Lymphoblastic Leukemia (ALL)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 276
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose of inotuzumab ozogamicin based on incidence of dose limiting toxicities (Phase I)
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of inotuzumab ozogamicin and to see how well it works when given together with combination chemotherapy in treating patients with acute lymphoblastic leukemia. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called N-acetyl-gamma-calicheamicin dimethyl hydrazide (CalichDMH). Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers CalichDMH to kill them. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy 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 inotuzumab ozogamicin together with combination chemotherapy may be a better treatment for acute lymphoblastic leukemia.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin (inotuzumab ozogamycin) in combination with low-intensity chemotherapy in elderly patients (age 60 or older) with acute lymphoblastic leukemia (ALL). (Phase I)
II. Evaluate the efficacy of inotuzumab ozogamycin in combination with low-intensity chemotherapy in elderly and unfit to receive intensive therapy patients with ALL. (Phase II)
III. To evaluate the side effects of the treatment. (Phase II)
IV. Evaluate the regimen efficacy in refractory-relapsed ALL. (Phase II)
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
- •Patients age 60 years or older with previously untreated ALL pre-B, Philadelphia chromosome (Ph-) negative or (Ph+) positive ALL Minimal prior therapy (less than 1 week of steroids, vincristine, and/or 1 dose of anthracycline or alkylating agents) are allowed.
- •Patients unfit ≥ 18 - < 60 years of age with previously untreated ALL pre- B, Philadelphia chromosome (Ph-) negative or (Ph+) positive ALL (includes patients initiated on first cycle of hyper-CVAD before cytogenetics known. These patients could have received one or two cycles of chemotherapy with or without other TKIs and still eligible.
- •These patients are defined as having at least one of the below comorbidities:
- •ECOG performance status ≥ 2
- •Severe cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
- •Severe pulmonary disorder (e.g., DLCO ≤ 65% or FEV1 ≤ 65%)
- •Creatinine clearance < 45 mL/min, and
- •Hepatic disorder with total bilirubin > 1.5 x upper limit of normal
- •If they achieved CR, they are assessable only for event-free and overall survival, or
- •If they failed to achieve CR, they are assessable for CR, event-free, and overall survival
- •Patients age 60 years and older unfit for intensive chemotherapy with one or more comorbidities (e.g., renal insufficiency, heart disease, cardio-vascular disease, uncontrolled hypertension, diabetes, respiratory problems, among others) and a PS of ≥
- •All ages of Jehovah's witness are eligible.
- •Zubrod performance status 0-
- •Adequate liver function (bilirubin < 1.95 mg/dL and SGPT or SGOT < 3 x upper limit of normal [ULN], unless considered due to tumor), and renal function (estimated creatinine clearance ≥50 mL/min/1.73 m2). Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is < 2.6 mg/dL and creatinine < 3 mg/dL.
- •Provision of written informed consent.
- •Patients in first remission are eligible.
- •Patients with refractory-relapsed ALL, Burkitt lymphoma, Burkitt-like lymphoma with 11q aberration, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma not otherwise specified with marrow involvementBof any age are eligible.
排除标准
- •Newly diagnosed Burkitt's Leukemia or Lymphoma, T-cell ALL or lymphoblastic lymphoma.
- •Patient with active heart disease (NYHA class > 3 as assessed by history and physical examination).
- •Patients with a cardiac ejection fraction (as measured by either MUGA or echocardiogram) < 40% are excluded.
- •Patients with active hepatitis are excluded.
- •Pregnant or breast-feeding women are excluded.
研究组 & 干预措施
Arm I (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm I
干预措施: Inotuzumab Ozogamicin (Biological)
Arm I (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm I
干预措施: Cyclophosphamide (Drug)
Arm I (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm I
干预措施: Cytarabine (Drug)
Arm I (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm I
干预措施: Methotrexate (Drug)
Arm I (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm I
干预措施: Vincristine (Drug)
Arm II (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm II
干预措施: Cyclophosphamide (Drug)
Arm II (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm II
干预措施: Mercaptopurine (Drug)
Arm II (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm II
干预措施: Methotrexate (Drug)
Arm II (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm II
干预措施: Vincristine (Drug)
Arm II (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm II
干预措施: Prednisone (Drug)
Arm III (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm III
干预措施: Cytarabine (Drug)
Arm III (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm III
干预措施: Rituximab (Biological)
Arm III (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm III
干预措施: Laboratory Biomarker Analysis (Other)
Arm III (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm III
干预措施: Methotrexate (Drug)
Arm III (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm III
干预措施: Vincristine (Drug)
Arm III (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm III
干预措施: Blinatumomab (Biological)
Arm I (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm I
干预措施: Laboratory Biomarker Analysis (Other)
Arm III (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm III
干预措施: Dexamethasone (Drug)
Arm I (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm I
干预措施: Rituximab (Biological)
Arm II (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm II
干预措施: Blinatumomab (Biological)
Arm II (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm II
干预措施: Rituximab (Biological)
Arm II (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm II
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm II
干预措施: Inotuzumab Ozogamicin (Biological)
Arm I (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm I
干预措施: Blinatumomab (Biological)
Arm III (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm III
干预措施: Inotuzumab Ozogamicin (Biological)
Arm II (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm II
干预措施: Cytarabine (Drug)
Arm I (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm I
干预措施: Prednisone (Drug)
Arm I (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm I
干预措施: Dexamethasone (Drug)
Arm I (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm I
干预措施: Mercaptopurine (Drug)
Arm II (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description Arm II
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Maximum tolerated dose of inotuzumab ozogamicin based on incidence of dose limiting toxicities (Phase I)
时间窗: 28 days
Defined as non-hematologic grade 3 or 4 toxicities during the first course. Toxicities will be monitored using the method of Thall, Simon, and Estey. Adverse events will be summarized and toxicity rate will be estimated with a 90% credible interval.
Response rate in refractory-relapsed acute lymphoblastic leukemia (ALL) (Phase II)
时间窗: Up to 5 years
The precise complete remission (CR) and marrow CR rate will be defined.
Survival in refractory-relapsed acute lymphoblastic leukemia (ALL) (Phase II)
时间窗: Up to 1 year
The median and 1-year survival rate will be defined. Kaplan and Meier product limit method will be used to estimate the overall survival (OS) along with the 95% confidence intervals for the median OS. Univariate and multivariate Cox proportional hazards regression models will be used to identify prognostic factors.
Progression free survival (PFS) in frontline elderly acute lymphoblastic leukemia (ALL) (Phase II)
时间窗: 2 years
Bayesian time-to-event model will be used. Kaplan and Meier product limit method will be used to estimate the PFS along with the 95% confidence intervals for the median PFS. Univariate and multivariate Cox proportional hazards regression models will be used to identify prognostic factors.
次要结局
未报告次要终点