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

Sponsor

University of Miami (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00878254

Collaborator

(none)

Enrollment

Location

Arm

221.2

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Mantle-Cell Lymphoma	Biological: G-CSF Drug: Rituximab Drug: Cyclophosphamide Drug: Cytarabine Drug: Doxorubicin Drug: Etoposide Drug: Ifosfamide Drug: Leucovorin Drug: Mesna Drug: Methotrexate Drug: Vincristine	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 25, 2009

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R-MACLO/IVAM 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 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. Other Names: Filgrastim Neupogen Drug: Rituximab 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. Other Names: Rituxan Drug: Cyclophosphamide 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. Other Names: Cytoxan Drug: Cytarabine Cytarabine 2 grams/m^2 IV on Days 1 and 2 of Cycles 2 and 4, per study protocol. Other Names: AraC Drug: Doxorubicin Doxorubicin 45 mg/m^2 IV bolus Day 1 of Cycles 1 and 3, per study protocol. Other Names: Adriamycin Drug: Etoposide Etoposide 60 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol. Other Names: VP16 Drug: Ifosfamide Ifosfamide 1.5 grams/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol. Other Names: Ifex Drug: Leucovorin 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. Other Names: Folinic acid Drug: Mesna Mesna 360 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol. Other Names: Mesnex Drug: Methotrexate 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. Other Names: MTX Drug: Vincristine 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. Other Names: Oncovin

Arm

Intervention/Treatment

Experimental: R-MACLO/IVAM

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

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.

Other Names:

Filgrastim

Neupogen

Drug: Rituximab

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.

Other Names:

Rituxan

Drug: Cyclophosphamide

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.

Other Names:

Cytoxan

Drug: Cytarabine

Cytarabine 2 grams/m^2 IV on Days 1 and 2 of Cycles 2 and 4, per study protocol.

Other Names:

AraC

Drug: Doxorubicin

Doxorubicin 45 mg/m^2 IV bolus Day 1 of Cycles 1 and 3, per study protocol.

Other Names:

Adriamycin

Drug: Etoposide

Etoposide 60 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.

Other Names:

VP16

Drug: Ifosfamide

Ifosfamide 1.5 grams/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.

Other Names:

Ifex

Drug: Leucovorin

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.

Other Names:

Folinic acid

Drug: Mesna

Mesna 360 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.

Other Names:

Mesnex

Drug: Methotrexate

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.

Other Names:

MTX

Drug: Vincristine

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.

Other Names:

Oncovin

Outcome Measures

Primary Outcome Measures

Rate of Progression-Free Survival (PFS) [Up to 8 years]
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.

Secondary Outcome Measures

Rate of Overall Survival (OS) [Up to 8 years]
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
Rate of Response to Protocol Therapy [Up to 8 years]
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.
Rate of Treatment-Related Toxicity in Study Participants [Up to 8 years]
Rate of adverse events, serious adverse events and other toxicities related to protocol therapy in study participants, as evaluated by treating physician.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.