A Randomized Phase II Study Testing the Combination of Inotuzumab Ozogamicin and Lower Dose Chemotherapy Plus Blinatumomab Compared to Usual Chemotherapy Plus Blinatumomab for Older Adults With B-Cell Acute Lymphoblastic Leukemia or B-Cell Lymphoblastic Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 68
- 试验地点
- 127
- 主要终点
- Event-free survival
研究概览
简要总结
This phase II trial compares the combination of inotuzumab ozogamicin and low intensity chemotherapy and blinatumomab to the usual chemotherapy with blinatumomab in treating patients with B-cell acute lymphoblastic leukemia or B-cell lymphoblastic lymphoma. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a drug, called CalichDMH. Inotuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD22 receptors, and delivers CalichDMH to kill them. Chemotherapy drugs 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. A monoclonal antibody, such as blinatumomab, is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving inotuzumab ozogamicin with chemotherapy and blinatumomab may help shrink the cancer and stop it from returning.
详细描述
PRIMARY OBJECTIVE:
I. To compare measurable residual disease (MRD) negative event-free survival (EFS) rate of the experimental arm (A) to standard arm (B) with EFS defined as time from randomization to occurrence of an event.
SECONDARY OBJECTIVES:
I. To determine overall response rate (complete response [CR] + complete remission with partial hematologic recovery [CRh] + complete remission with incomplete platelet counts [CRp] + complete remission with incomplete blood count recovery [CRi]) at designated time points (after cycle 1, after cycle 2, end of blinatumomab [blina]-1, end of intensive phase/blina-4) in each treatment arm.
II. To determine rate of flow cytometry MRD-negativity (undetectable or detectable < 10^-4) at designated time points (after cycle 1, after cycle 2, end of blina-1, end of intensive phase/blina-4) in each treatment arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PRE-REGISTRATION ELIGIBILITY CRITERIA (STEP 0)
- •Research bone marrow or peripheral blood submission
- •* This bone marrow or peripheral blood submission is mandatory prior to registration/randomization as baseline for real-time MRD analysis. The bone marrow sample should be from the first aspiration (i.e., first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be obtained as soon after pre-registration as possible
- •REGISTRATION ELIGIBILITYCRITERIA (STEP 1)
- •Diagnosis of B-cell acute lymphoblastic leukemia (ALL) per World Health Organization (WHO) 2016 criteria. Patients must have >= 20% blasts in the bone marrow or blood. Patients with lymphoblastic lymphoma (LBL) with <20% blasts in the marrow are permitted.
- •* T-cell ALL/LBL, Philadelphia-chromosome positive B-cell (as determined by fluorescence in situ hybridization [FISH], cytogenetics, or reverse transcriptase polymerase chain reaction [RT-PCR]), and Burkitt's like leukemia/lymphoma (mature B-ALL) are not eligible
- •Must be CD22 positive by local assessment (>= 20% by immunohistochemistry or flow cytometry). Patients are eligible regardless of CD20 status but CD20 expression should be assessed at diagnosis by flow cytometry or immunohistochemistry
- •Patients with symptomatic central nervous system (CNS) disease are not eligible. CNS assessment is not required for eligibility determination if asymptomatic
- •Patients must have >= 5% blasts in the bone marrow or blood. Patients with lymphoblastic lymphoma (LBL) without marrow involvement (>= 5% blasts) are not eligible
- •No prior chemotherapy for ALL except for hydroxyurea (no limit), steroids limited to 7 days, ATRA (no limit), vincristine (single dose), and/or intra-thecal chemotherapy. Leukapheresis is permitted. Palliative radiation to doses 24 Gy or less is permitted. Patients being treated with chronic steroids for other reasons (autoimmune disorder, etc.) are eligible
- •Age >= 50 years
- •Eastern Cooperative Oncology Group (ECOG) performance status =<
- •ECOG 3 permitted if related to disease
- •Creatinine =< 2.0 g/dL
- •Total bilirubin =< 1.5 x upper limit of normal (ULN)
- •* Except in the event of: 1) Gilbert disease, in which case total bilirubin must be =< 2 x ULN, or 2) elevated bilirubin believed by investigator to be due to leukemic infiltration, in which case total bilirubin must be =< 2 x ULN
- •AST / ALT =< 2.5 x upper limit of normal (ULN)
- •Cardiac ejection fraction (as measured by multigated acquisition scan [MUGA] or echocardiogram) > 40%
- •No clinically relevant liver disease (such as cirrhosis, active hepatitis, alcohol use disorder or sinusoidal occlusive syndrome), which in the opinion of the treating physician would make this protocol unreasonably hazardous
- •Patients with known hepatitis B virus (HBV) infection are eligible if they are on effective HBV suppressive therapy with undetectable HBV viral load and there is no clinically relevant liver disease present (related or unrelated to HBV-related liver damage)
- •Patients with known history of hepatitis C virus (HCV) infection are eligible if they have cleared the infection spontaneously or via eradication therapy (HCV viral load undetectable) and there is no clinically relevant liver disease present (related or unrelated to HCV-related liver damage)
- •Physicians should consider whether any of the following may render the patient inappropriate for this protocol:
- •Medical condition such as uncontrolled diabetes mellitus, uncontrolled cardiac disease, and uncontrolled pulmonary disease.
- •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- •Patients with a "currently active" second malignancy other than non-melanoma skin cancers, early stage prostate cancer, cervical carcinoma in situ, or other cancer for which standard of care would be observation (not requiring treatment). Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for >= 1 year, or if the cancer has been surgically resected and considered cured. Patients with a history of multiple myeloma with absence of serum paraprotein for >= 1 year are not considered to have a "currently active" malignancy.
- •Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Include as applicable: Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom)
排除标准
- •Physicians should consider whether any of the following may render the patient inappropriate for this protocol:
- •Medical condition such as uncontrolled diabetes mellitus, uncontrolled cardiac disease, and uncontrolled pulmonary disease.
- •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- •Patients with a "currently active" second malignancy other than non-melanoma skin cancers, early stage prostate cancer, cervical carcinoma in situ, or other cancer for which standard of care would be observation (not requiring treatment). Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for >= 1 year, or if the cancer has been surgically resected and considered cured. Patients with a history of multiple myeloma with absence of serum paraprotein for >= 1 year are not considered to have a "currently active" malignancy.
- •REGISTRATION EXCLUSION CRITERIA (STEP 1)
- •Patients with symptomatic central nervous system (CNS) disease are not eligible. CNS assessment is not required for eligibility determination if asymptomatic
研究组 & 干预措施
Arm A (inotuzumab ozogamicin, chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
Arm A (inotuzumab ozogamicin, chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Dexamethasone (Drug)
Arm A (inotuzumab ozogamicin, chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Inotuzumab Ozogamicin (Biological)
Arm A (inotuzumab ozogamicin, chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Methylprednisolone (Drug)
Arm A (inotuzumab ozogamicin, chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Rituximab (Biological)
Arm B (chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Rituximab (Biological)
Arm A (inotuzumab ozogamicin, chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Cytarabine (Drug)
Arm A (inotuzumab ozogamicin, chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Vincristine (Drug)
Arm A (inotuzumab ozogamicin, chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Methotrexate (Drug)
Arm A (inotuzumab ozogamicin, chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Prednisone (Drug)
Arm B (chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Vincristine (Drug)
Arm A (inotuzumab ozogamicin, chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Mercaptopurine (Drug)
Arm B (chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
Arm B (chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Dexamethasone (Drug)
Arm B (chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Methotrexate (Drug)
Arm B (chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Cytarabine (Drug)
Arm B (chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Prednisone (Drug)
Arm B (chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Methylprednisolone (Drug)
Arm B (chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Mercaptopurine (Drug)
Arm B (chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment.
Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Event-free survival
时间窗: From randomization to failure to achieve measurable residual disease (MRD)-negative complete response (CR) after two cycles of chemotherapy, relapse, or death from any causes, assessed at 2 months (after 2 cycles of treatment)
Will be evaluated using the methods of Kaplan-Meier as well as Cox regression models.
Event-free survival
时间窗: From randomization to failure to achieve MRD negative complete response (CR) after two cycles of chemotherapy, relapse, removal from protocol therapy due to toxicity prior to achievement of MRD assessed at 3 months.
Will be evaluated using the methods of Kaplan-Meier as well as Cox regression models.
次要结局
- Disease-free survival(Time from achieving a CR/ complete remission with incomplete blood count recovery (CRi) to the time of relapse and/or death, assessed up to 5 years)
- Overall survival(From randomization to the time of death due to any cause, assessed up to 5 years)
- Overall response rate(Up to 5 years)
- MRD-negativity rate(Up to end of cycle 8 (1 cycle = 28 days))
- Event-free survival(Up to 5 years)
- Complete remission rate(Up to 5 years)
- Rate of grade 3-5 adverse events(Up to 5 years)