Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated Mantle Cell Lymphoma - Full Text View

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 Sylvester Comprehensive Cancer Center:

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

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

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

Locations

United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33186

Sponsors and Collaborators

University of Miami Sylvester Comprehensive Cancer Center

Investigators

Principal Investigator:

Izidore S. Lossos, MD

University of Miami Sylvester Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00878254 History of Changes
Other Study ID Numbers:	EPROST-20080803, SCCC-2008043
Study First Received:	April 7, 2009
Last Updated:	March 11, 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
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 May 23, 2013