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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00450801
First received: March 20, 2007
Last updated: August 13, 2013
Last verified: August 2013
  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. Biological therapies, such as thalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving rituximab together with combination chemotherapy and thalidomide may kill more cancer cells.

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


Condition Intervention Phase
Lymphoma
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Doxorubicin
Drug: Etoposide
Drug: Ifosfamide
Drug: Leucovorin
Drug: Methotrexate
Drug: Thalidomide
Drug: Vincristine
Drug: Mesna
Drug: Filgrastim (G-CSF)
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 (Maclo/Ivam) in Patients With Previously Untreated Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by University of Miami Sylvester Comprehensive Cancer Center:

Primary Outcome Measures:
  • Progression-free survival at 6, 12, 18, and 24 months [ Time Frame: 6, 12, 18, and 24 months ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: April 2004
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MACLO IVAM Drug: Rituximab
Rituximab 375 mg/m2 IV, Days 1, 4 Cycles
Other Name: Rituxan
Drug: Cyclophosphamide
Cyclophosphamide 800 mg/m2 IV, Day 1, Cyclophosphamide 200 mg/m2 IV Days 2 - 5, Cycles 1 and 3. Cyclophosphamide will be given in 100 cc NS IV over 30 minutes.
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, Cycles 2 and 4
Other Name: VP16
Drug: Ifosfamide
Ifosfamide 1.5 grams/m2 IV QD x 5 days, Cycles 2 and 4
Other Name: Ifex
Drug: Leucovorin
Leucovorin 180 mg/m2 IV beginning 36 hours after start of methotrexate infusion and then 12 mg/m2 IV every 6 hours until methotrexate level is below 0.01 nM. Day 10, Cycles 1 and 3.
Other Name: Folinic Acid
Drug: Methotrexate
Methotrexate 1,200 mg/m2 in 250 cc D5W IV over 1 hour followed by Methotrexate 5,520 mg/m2 in 1,000 cc D5W by continuous infusion over 23 hours (240 mg/m2 every hour for 23 hours). Day 10, Cycles 1 and 3.
Other Name: amethopterin
Drug: Thalidomide
Maintenance therapy.
Other Name: Thalomid
Drug: Vincristine
Vincristine 1.5 mg/m2 IVP (maximum of 2 mg), Day 8 , Cycles 1 and 3.
Other Name: Oncovin
Drug: Mesna
Mesna 360 mg/m2 IV every 3 hours x 5 days, Cycles 2 and 4
Other Name: Mesnex
Drug: Filgrastim (G-CSF)
G-CSF 480 mcg SQ starting Day 13 (Cycles 1 and 3), Day 7 (Cycles 2 and 4)
Other Name: Neupogen

Detailed Description:

OBJECTIVES:

Primary

  • Determine the progression-free survival of patients with previously untreated mantle cell lymphoma treated with rituximab and combination chemotherapy comprising vincristine, doxorubicin hydrochloride, cyclophosphamide, methotrexate, ifosfamide, cytarabine, and etoposide followed by thalidomide.

Secondary

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

OUTLINE: Patients receive rituximab IV and doxorubicin hydrochloride IV over 3-5 minutes on day 1, vincristine IV on days 1 and 8, cyclophosphamide IV over 30 minutes on days 1-5, methotrexate IV over 24 hours on day 10, and leucovorin calcium IV every 6 hours beginning on day 11 and continuing until the level of methotrexate in the blood is within a safe range. Patients 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, patients receive rituximab IV on day 1 (i.e., the day ANC reaches 1,500/mm^3), ifosfamide IV over 1 hour on days 1-5, cytarabine IV over 3 hours every 12 hours on days 1 and 2, and etoposide IV over 1 hour on days 1-5. Patients also receive G-CSF SC once daily beginning on day 7 and continuing until blood counts recover. Approximately 2-3 weeks later, patients receive another course of therapy as above.

Patients in complete remission after 2 courses of rituximab and combination chemotherapy receive oral thalidomide daily. Treatment with thalidomide continues for 1 year 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 annually thereafter.

PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.

  Eligibility

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

Inclusion Criteria:

DISEASE CHARACTERISTICS:

  • Histologically confirmed mantle cell lymphoma

    • All stages allowed
  • 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/or SGPT < 2.5 times upper limit of normal (unless due to lymphomatous involvement)
  • Creatinine < 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception during and for ≥ 4 weeks after completion of study treatment (if receiving thalidomide)
  • No other concurrent active malignancies, except for in situ carcinoma of the cervix or basal cell carcinoma of the skin

Exclusion Criteria:

Grade 3-4 cardiac failure

  • LVEF that is less than ≥ 50%
  • psychological, familial, sociological, or geographical conditions that would preclude study compliance
  • known history of HIV or AIDS
  • hepatitis or hepatitis B virus infection

PRIOR CONCURRENT THERAPY:

  • Any 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: NCT00450801

Locations
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami Sylvester Comprehensive Cancer Center
Investigators
Study Chair: Izidore S. Lossos, MD University of Miami Sylvester Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00450801     History of Changes
Other Study ID Numbers: UMIAMI-20030165, SCCC-2003027, WIRB-20051242
Study First Received: March 20, 2007
Last Updated: August 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami Sylvester Comprehensive Cancer Center:
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
Thalidomide
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

ClinicalTrials.gov processed this record on July 23, 2014