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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Miami
Sponsor:
Information provided by (Responsible Party):
Izidore Lossos, University of Miami
ClinicalTrials.gov Identifier:
NCT00878254
First received: April 7, 2009
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

RATIONALE: To evaluate the efficacy of a new high intensity chemotherapy regimen with rituximab maintenance in patients with newly diagnosed mantle cell lymphoma

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy followed by rituximab works in treating patients with previously untreated mantle cell lymphoma.


Condition Intervention Phase
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 Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 8 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 22
Study Start Date: March 2009
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R-MACLO/IVAM Biological: G-CSF
G-CSF 480 mcg SQ starting on day 13 (Cycle 1, 3) and day 7 (Cycle 2, 4)
Other Names:
  • Filgrastim
  • Neupogen
Drug: Rituximab
375 mg/m2 IV according to standard protocol; Day 1 for 4 Cycles
Other Name: Rituxan
Drug: Cyclophosphamide
Cyclophosphamide 800 mg/m2 IV on Day 1 and 200 mg/m2 IV on Days 2 - 5 for Cycle 1, 3
Other Name: Cytoxan
Drug: Cytarabine
Cytarabine 2 grams/m2 IV every 12 hours x 4 doses, days 1 and 2, Cycles 2 and 4
Other Name: AraC
Drug: Doxorubicin
Doxorubicin 45 mg/m2 IV bolus Day 1 , Cycles 1 and 3
Other Name: Adriamycin
Drug: Etoposide
Etoposide 60 mg/m2 IV daily x 5 days, Days 1 - 5, Cycles 2 and 4
Other Name: VP16
Drug: Ifosfamide
Ifosfamide 1.5 grams/m2 IV QD x 5 days, Days 1 - 5, Cycles 2 and 4
Other Name: Ifex
Drug: Leucovorin
Leucovorin 100 mg/m2 IV beginning 36 hours after start of methotrexate infusion and then 10 mg/m2 IV every 6 hours until methotrexate level is below 0.05 nM. Day 10, Cycles 1 and 3.
Other Name: Folinic acid
Drug: Mesna
Mesna 360 mg/m2 IV every 3 hours x 5 days, Days 1 - 5 Cycles 2 and 4
Other Name: Mesnex
Drug: Methotrexate
Methotrexate 1,200 mg/m2 in 250 mL D5W IV over 1 hour followed by Methotrexate 3,000 mg/m2 in 1,000 mL D5W by continuous infusion over 23 hours (130 mg/m2 every hour for 23 hours). Day 10 Cycles 1 and 3
Drug: Vincristine
Vincristine 1.5 mg/m2 IVP (maximum of 2 mg) days 1 and 8 for Cycles 1 and 3
Other Name: Oncovin

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate progression-free survival of patients with previously untreated mantle cell lymphoma treated with rituximab in combination with methotrexate, doxorubicin, cyclophosphamide, leucovorin, vincristine, ifosfamide, etoposide, cytarabine and mesna (R-MACLO/IVAM)

Secondary

  • To evaluate overall survival of patients treated with this regimen.
  • To evaluate the response rate in patients treated with this regimen.
  • To evaluate the toxicity of this regimen in these patients.

OUTLINE:

Cycle 1, patients will receive rituximab IV, doxorubicin IV bolus, vincristine IVP on day 1; cyclophosphamide IV on day 1-5; vincristine IVP on day 8; methotrexate IV follow by methotrexate via continuous infusion on day 10, then leucovorin 100mg/m^2 IV, followed by leucovorin 10mg/m^2 IV until methotrexate level is below 0.01 nM on day 11. Patients will receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 13 and continuing until blood counts recover.

When absolute neutrophil count (ANC) reaches 1,500/mm^3 two consecutive times, patients will start cycle 2. Patients will receive rituximab IV on day 1; cytarabine IV on day 1 and 2; ifosfamide IV, mesna IV, etoposide IV on day 1-5; and G-CSF SC daily beginning on day 7 and continuing until ANC is greater than 1,000 cells/mm^3.

Approximately 7-14 days later, patients receive another course of therapy as above.

Patients who achieve complete remission after completion of course 4 receive rituximab IV once weekly for 4 weeks. Treatment repeats every 6 months for up to 3 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3-5 years, and then yearly thereafter.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed mantle cell lymphoma

    • Previously untreated disease
  • Measurable or evaluable disease
  • No CNS involvement

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 6 months
  • Bilirubin < 3 mg/dL
  • SGOT and SGPT < 2.5 times upper limit of normal (unless due to lymphomatous involvement)
  • Serum creatinine < 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No grade 3-4 cardiac failure
  • LVEF ≥ 50%
  • No known history of HIV or AIDS
  • No hepatitis or hepatitis B virus infection
  • No other concurrent active malignancy, except carcinoma in situ of the cervix and basal cell carcinoma of the skin
  • No psychological, familial, sociological, or geographical conditions that would prohibit treatment and/or medical follow-up required to comply with study protocol

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, immunotherapy, or radiotherapy for this lymphoma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00878254

Locations
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33186
Contact: Izidore S. Lossos, MD    305-243-4785    ilossos@med.miami.edu   
Contact: University of Miami Sylvester Comprehensive Cancer Center    866-574-5124    sylvester@emergingmed.com   
Principal Investigator: Izidore S Lossos, MD         
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Izidore S. Lossos, MD University of Miami
  More Information

Additional Information:
No publications provided

Responsible Party: Izidore Lossos, Professor, University of Miami
ClinicalTrials.gov Identifier: NCT00878254     History of Changes
Other Study ID Numbers: 20080803, SCCC-2008043
Study First Received: April 7, 2009
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Cytarabine
Doxorubicin
Etoposide
Etoposide phosphate
Ifosfamide
Isophosphamide mustard
Liposomal doxorubicin
Methotrexate
Rituximab
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on November 27, 2014