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
Overview
- Phase
- Phase 2
- Intervention
- G-CSF
- Conditions
- Mantle-Cell Lymphoma
- Sponsor
- University of Miami
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival (PFS)
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
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).
Investigators
Izidore Lossos, MD
Professor
University of Miami
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
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.
Intervention: G-CSF
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.
Intervention: Rituximab
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.
Intervention: Cyclophosphamide
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.
Intervention: Cytarabine
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.
Intervention: Doxorubicin
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.
Intervention: Etoposide
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.
Intervention: Ifosfamide
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.
Intervention: Leucovorin
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.
Intervention: Mesna
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.
Intervention: Methotrexate
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.
Intervention: Vincristine
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- 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)