Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated Mantle Cell Lymphoma

Study Overview
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Brief Summary
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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).

Official Title
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Phase II Study of Rituximab in Combination With Methotrexate, Doxorubicin, Cyclophosphamide, Leucovorin, Vincristine, Ifosfamide, Etoposide, Cytarabine and Mesna (R-MACLO/VAM) in Patients With Previously Untreated Mantle Cell Lymphoma

Conditions
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Mantle-Cell Lymphoma

Intervention / Treatment
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* Biological: G-CSF
* Drug: Rituximab
* Drug: Cyclophosphamide
* Drug: Cytarabine
* Drug: Doxorubicin
* Drug: Etoposide
* Drug: Ifosfamide
* Drug: Leucovorin
* Drug: Mesna
* Drug: Methotrexate
* Drug: Vincristine


Participation Criteria
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Eligibility Criteria
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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 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. 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 < 50. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R-MACLO/IVAM<br>Four 21-day cycles, followed by Maintenance Therapy as follows: Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin, and G-CSF per study protocol. Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF per study protocol. Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years, per study protocol. | Biological: G-CSF<br>* Granulocyte-colony stimulating factor (G-CSF) 480 mcg subcutaneously (SQ) starting on Day 13 of Cycles 1 and 3; and Day 7 of Cycles 2 and 4, per study protocol.<br>* Other names: Neupogen;Drug: Rituximab<br>* Rituximab 375 mg/m^2 intravenously (IV) on Day 1 for 4 Cycles, per study protocol. For study participants achieving complete remission, during maintenance therapy every 6 months for up to three years, per study protocol.<br>* Other names: Rituxan;Drug: Cyclophosphamide<br>* Cyclophosphamide 800 mg/m^2 IV on Day 1 and 200 mg/m^2 IV on Days 2 through 5 of Cycles 1 and 3, per study protocol.<br>* Other names: Cytoxan;Drug: Cytarabine<br>* Cytarabine 2 grams/m^2 IV on Days 1 and 2 of Cycles 2 and 4, per study protocol.<br>* Other names: AraC;Drug: Doxorubicin<br>* Doxorubicin 45 mg/m^2 IV bolus Day 1 of Cycles 1 and 3, per study protocol.<br>* Other names: Adriamycin;Drug: Etoposide<br>* Etoposide 60 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.<br>* Other names: VP16;Drug: Ifosfamide<br>* Ifosfamide 1.5 grams/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.<br>* Other names: Ifex;Drug: Leucovorin<br>* Leucovorin: 100 mg/m^2 IV beginning 36 (+/-4) hours after start of Methotrexate infusion, and then 10 mg/m^2 at 6 hour (+/- 30 min) intervals until Methotrexate level is < 0.1 µmol/L during Cycles 1 and 3 per study protocol.<br>* Other names: Folinic acid;Drug: Mesna<br>* Mesna 360 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.<br>* Other names: Mesnex;Drug: Methotrexate<br>* Methotrexate 1,200 mg/m^2 in 250 mL D5W IV over 1 hour, followed by Methotrexate 3,000 mg/m^2 in 1,000 mL D5W by continuous infusion over 23 (+/-2) hours on Day 10 of Cycles 1 and 3, per study protocol.<br>* Other names: MTX;Drug: Vincristine<br>* Vincristine 1.5 mg/m^2 IV push (maximum of 2 mg) on Days 1 and 8 of Cycles 1 and 3, per study protocol.<br>* Other names: Oncovin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Progression-Free Survival (PFS) | Rate of Progression-Free Survival (PFS) in study participants. 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. | Up to 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Overall Survival (OS) | Rate of Overall Survival (OS) in study participants. OS is defined as the length of time from the start of treatment until death from any cause. OS will be evaluated by treating physician from staging CT or PET scans | Up to 8 years | 
| Rate of Response to Protocol Therapy | Rate of response to protocol therapy in study participants. Response is defined as complete response (CR), complete response/unconfirmed (CRu) or partial response (PR) to protocol therapy according to criteria assignable to Non-Hodgkin's Lymphoma (NHL). Response assessment will be done by CT and Positron emission tomography (PET) scans, and bone marrow biopsy/aspirate, if clinically indicated. | Up to 8 years | 
| Rate of Treatment-Related Toxicity in Study Participants | Rate of adverse events, serious adverse events and other toxicities related to protocol therapy in study participants, as evaluated by treating physician. | Up to 8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Hodgkin's Lymphoma, MCL, NHL