Phase II Study of Rituximab in Combination With Methotrexate, Doxorubicin, Cyclophosphamide, Leucovorin, Vincristine, Ifosfamide, Etoposide, Cytarabine and Mesna (R-MACLO/IVAM) in Patients With Previously Untreated Mantle Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The investigator(s) hypothesize that Rituximab together with combination chemotherapy, followed by Rituximab maintenance therapy, will provide better disease control with improved response rates and overall survival in patients with previously untreated Mantle Cell Lymphoma (MCL).
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 untreated, histologically confirmed mantle cell lymphoma,
- •Measurable or evaluable disease (at least one site with >1.5 cm in diameter
- •All stages are eligible
- •Age > 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- •Adequate hepatic function:
- •Bilirubin < 3 mg/dL
- •Transaminases (serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate-pyruvate transaminase (SGPT)) < than 2.5 times the upper limit of normal for the institution, unless due to lymphomatous involvement
- •Serum creatinine< 1.5 mg/dl
- •Ability to give informed consent
- •Women of childbearing potential must have a negative pregnancy test within 72 hours of entering into the study. Males and females must agree to use adequate birth control if conception is possible during the study. Women must avoid pregnancy and men avoid fathering children while in the study.
- •Life expectancy greater than 6 months.
排除标准
- •Previous chemotherapy, immunotherapy or radiotherapy for this mantle cell lymphoma
- •Concurrent active malignancies, with the exception of in situ carcinoma of the cervix and basal cell carcinoma of the skin.
- •Grade 3 or 4 cardiac failure and/or ejection fraction <
- •Psychological, familial, sociological or geographical conditions that do not permit treatment and/or medical follow-up required to comply with the study protocol.
- •Patients with a known history of human immunodeficiency virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS).
- •Presence of hepatitis or hepatitis B virus (HBV) infection.
- •Pregnant or breast-feeding women.
- •Central Nervous System (CNS) involvement.
研究组 & 干预措施
R-MACLO/IVAM Group
Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
- Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
- Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival.
干预措施: G-CSF (Biological)
R-MACLO/IVAM Group
Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
- Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
- Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival.
干预措施: Rituximab (Drug)
R-MACLO/IVAM Group
Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
- Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
- Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival.
干预措施: Cyclophosphamide (Drug)
R-MACLO/IVAM Group
Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
- Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
- Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival.
干预措施: Cytarabine (Drug)
R-MACLO/IVAM Group
Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
- Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
- Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival.
干预措施: Doxorubicin (Drug)
R-MACLO/IVAM Group
Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
- Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
- Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival.
干预措施: Etoposide (Drug)
R-MACLO/IVAM Group
Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
- Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
- Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival.
干预措施: Ifosfamide (Drug)
R-MACLO/IVAM Group
Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
- Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
- Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival.
干预措施: Leucovorin (Drug)
R-MACLO/IVAM Group
Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
- Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
- Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival.
干预措施: Mesna (Drug)
R-MACLO/IVAM Group
Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
- Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
- Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival.
干预措施: Methotrexate (Drug)
R-MACLO/IVAM Group
Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
- Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
- Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival.
干预措施: Vincristine (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to 12 years
Progression-Free Survival (PFS) among study participants. PFS is defined as the time in years from start of treatment to the earliest one of the following events: relapse (in patients who achieve complete response), disease progression (in patients with partial response or stable disease), or death. PFS will be evaluated by treating physician from staging Computed Tomography (CT) or Positron Emission Tomography (PET) scans.
Progression-Free Survival (PFS) Rate at 5 Years Using Kaplan-Meier Method
时间窗: 5 years
Progression-Free Survival (PFS) rate at 5 years estimated by the Kaplan-Meier method will be reported as percentage probability of participants alive without relapse or disease progression at 5 years after starting study therapy. PFS is defined as the time from start of treatment to the earliest one of the following events: relapse (in patients who achieve complete response), disease progression (in patients with partial response or stable disease), or death. PFS will be evaluated by treating physician from staging Computed Tomography (CT) or Positron Emission Tomography (PET) scans.
次要结局
- Overall Survival (OS) Rate at 5 Years Using Kaplan-Meier Method(5 years)
- Rate of Response to Study Therapy(Up to 8 years)
- Number of Participants Experiencing Treatment-Related Serious Adverse Events During R-MACLO/IVAM Induction Therapy(Up to 4 months)
- Number of Participants Experiencing Treatment-Related Adverse Events During R-MACLO/IVAM Induction Therapy(Up to 4 months)
研究者
Izidore Lossos, MD
Professor
University of Miami