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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Miami
Sponsor:
Information provided by (Responsible Party):
University of Miami
ClinicalTrials.gov Identifier:
NCT00878254
First received: April 7, 2009
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating mantle cell lymphoma.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy 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, Vincritine, Ifosfamide, Etoposide, Cytarabine and Mesna (R-MACLO/VAM) in Patients With Previously Untreaded 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 Study Completion Date: December 2017
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 12 (Cycle 1), day 7 (Cycle 2), day 13 (Cycle 3), day 7 (Cycle 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, Day 1 - for 4 Cycles and 200 mg/m2 IV, Days 2 - 5 for 4 Cycles
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 and combination chemotherapy comprising methotrexate, doxorubicin hydrochloride, cyclophosphamide, leucovorin calcium, vincristine sulfate, ifosfamide, etoposide, and cytarabine.

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:

  • Courses 1 and 3: Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1; vincristine sulfate IV on days 1 and 8; cyclophosphamide IV over 30 minutes on days 1-5; methotrexate IV continuously over 24 hours on day 10; leucovorin calcium IV every 6 hours beginning beginning 36 hours after start of methotrexate infusion and continuing until methotrexate level is below 0.05 nM; and filgrastim (G-CSF) subcutaneously (SC) beginning on day 13 and continuing until blood counts recover.
  • Courses 2 and 4: Patients receive rituximab IV on day 1; cytarabine IV over 3 hours every 12 hours on days 1 and 2; ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5; and G-CSF SC beginning on day 7 and continuing until blood counts recover.

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 monthly for 3 months, 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 Sylvester Comprehensive Cancer Center - Miami Recruiting
Miami, Florida, United States, 33186
Contact: Izidore S. Lossos, MD    866-574-5124      
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: University of Miami
ClinicalTrials.gov Identifier: NCT00878254     History of Changes
Other Study ID Numbers: UMIAMI-20080803, SCCC-2008043
Study First Received: April 7, 2009
Last Updated: February 28, 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
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Mesna
Levoleucovorin
Cyclophosphamide
Cytarabine
Methotrexate
Rituximab
Ifosfamide
Isophosphamide mustard
Etoposide phosphate
Doxorubicin
Etoposide
Vincristine
Leucovorin
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on July 24, 2014