S0213 Chemotherapy Plus Rituximab in Treating Patients With Mantle Cell Lymphoma - Full Text View

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining rituximab with chemotherapy may kill more cancer cells.

PURPOSE: Phase II pilot study to study the effectiveness of combining chemotherapy with rituximab in treating patients who have newly diagnosed mantle cell lymphoma.

Condition	Intervention	Phase
Lymphoma	Biological: filgrastim Biological: rituximab Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: doxorubicin Drug: leucovorin Drug: methotrexate Drug: vincristine	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Pilot Trial of Hyper-CVAD and Methotrexate/ARA C Plus Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma

Resource links provided by NLM:

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:

Progression-free Survival [ Time Frame: assessed after cycle 4, after completion of treatment, then every 3 months until 1 year after registration ] [ Designated as safety issue: No ]
Progression-Free Survival (PFS) rate at 1 year. PFS measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is a 50% increase in the sum of products of greatest diameters (SPD) of target measurable lesions over the smallest sum observed if a complete response (confirmed, or unconfirmed) was not previously achieved; appearance of a new lesion/site; unequivocal progression of non-measurable disease; or death due to disease without prior documentation of progression.

Secondary Outcome Measures:

Response [ Time Frame: assessed after cycle 4 and after completion of treatment (168 days) ] [ Designated as safety issue: No ]
Complete (CR), complete unconfirmed (CRU) and partial responses (PR). CR is complete disappearance of all measurable and non-measurable disease with the exception of nodes; no new lesions; previously enlarged organs must have regressed in size; and if bone marrow positive at baseline, it must be negative. CRU is complete disappearance of all measurable and non-measurable disease; regressed, non-palpable organs; and one or more exceptions not qualifying for CR (see protocol section 10). PR applies to patients with at least one measurable lesion who do not qualify for CR or CRU. PR is a 50% decrease in sum of products of greatest diameters (SPD) for up to six identified dominant lesions identified at baseline; no new lesions; no increase in the size of liver, spleen or other nodes; and splenic and hepatic nodules must have regressed in size by at least 50% in SPD.
Overall Survival [ Time Frame: assessed after cycle 4, after completion of treatment, then every 3 months for 2 years, then every 6 months thereafter until 5 years ] [ Designated as safety issue: No ]
Overall Survival rate at 1 year. Time to death is from date of registration to date of death due to any cause.

Enrollment:	56
Study Start Date:	September 2002
Study Completion Date:	June 2011
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Hyper-CVAD + MTX/Ara-C + Rituximab 21-day cycles of Hyper-CVAD and high-dose methotrexate/cytarabine are alternated beginning with Hyper-CVAD for a maximum of 8 cycles. Rituximab is given for cycles 1-6. Hyper-CVAD (cycles 1,3,5,7): rituximab 375 mg/m^2 on day 1, mesna 600 mg/m^2 on days 2-4, cyclophosphamide 300 mg/m^2 on days 2-4, doxorubicin 16.6 mg/m^2/day on days 5-7, vincristine 1.4 mg/m^2 on days 5 and 12, dexamethasone 40 mg on days 2-5 and 12-15, and filgrastim 5 ug/kg on days 8-21. Methotrexate/Ara-C (cycles 2,4,6,8): rituximab 375 mg/m^2 on day 1, methotrexate 1000 mg/m^2 over days 2-3, Ara-C 12 g/m^2 over days 3-4, leucovorin 170 mg over days 3-5, and G-CSF 5 ug/kg on days 5-21.	Biological: filgrastim 5 ug/kg Other Name: G-CSF Biological: rituximab 375 mg/m^2 on day 1 of cycles 1-6 Drug: cyclophosphamide 300 mg/m^2 on days 2-4 of cycles 1,3,5,7 Other Name: cytoxan Drug: cytarabine 12 g/m^2 over days 3-4 of cycles 2,4,6,8 Other Name: Ara-C Drug: dexamethasone 40 mg on days 2-5 and 12-15 of cycles 1,3,5,7 Drug: doxorubicin 16.6 mg/m^2/day for days 5-7 of cycles 1,3,5,7 Other Name: adriamycin Drug: leucovorin 170 mg over days 3-5 of cycles 2,4,6,8 Other Name: leucovorin calcium Drug: methotrexate 1000 mg/m^2 over days 2-3 of cycles 2,4,6,8 Other Name: MTX Drug: vincristine 1.4 mg/m^2 on days 5 and 12 of cycles 1,3,5,7 Other Name: vincristine sulfate

Arms

Assigned Interventions

Experimental: Hyper-CVAD + MTX/Ara-C + Rituximab

21-day cycles of Hyper-CVAD and high-dose methotrexate/cytarabine are alternated beginning with Hyper-CVAD for a maximum of 8 cycles. Rituximab is given for cycles 1-6.

Hyper-CVAD (cycles 1,3,5,7): rituximab 375 mg/m^2 on day 1, mesna 600 mg/m^2 on days 2-4, cyclophosphamide 300 mg/m^2 on days 2-4, doxorubicin 16.6 mg/m^2/day on days 5-7, vincristine 1.4 mg/m^2 on days 5 and 12, dexamethasone 40 mg on days 2-5 and 12-15, and filgrastim 5 ug/kg on days 8-21.

Methotrexate/Ara-C (cycles 2,4,6,8): rituximab 375 mg/m^2 on day 1, methotrexate 1000 mg/m^2 over days 2-3, Ara-C 12 g/m^2 over days 3-4, leucovorin 170 mg over days 3-5, and G-CSF 5 ug/kg on days 5-21.

Biological: filgrastim

5 ug/kg

Other Name: G-CSF

Biological: rituximab

375 mg/m^2 on day 1 of cycles 1-6

Drug: cyclophosphamide

300 mg/m^2 on days 2-4 of cycles 1,3,5,7

Other Name: cytoxan

Drug: cytarabine

12 g/m^2 over days 3-4 of cycles 2,4,6,8

Other Name: Ara-C

Drug: dexamethasone

40 mg on days 2-5 and 12-15 of cycles 1,3,5,7

Drug: doxorubicin

16.6 mg/m^2/day for days 5-7 of cycles 1,3,5,7

Other Name: adriamycin

Drug: leucovorin

170 mg over days 3-5 of cycles 2,4,6,8

Other Name: leucovorin calcium

Drug: methotrexate

1000 mg/m^2 over days 2-3 of cycles 2,4,6,8

Other Name: MTX

Drug: vincristine

1.4 mg/m^2 on days 5 and 12 of cycles 1,3,5,7

Other Name: vincristine sulfate

Detailed Description:

OBJECTIVES:

Determine the 1-year progression-free survival probability in patients with previously untreated mantle cell lymphoma treated with courses of rituximab and cyclophosphamide, doxorubicin, vincristine, and dexamethasone alternating with courses of rituximab and high-dose cytarabine and methotrexate with leucovorin calcium.
Determine the response rate (complete unconfirmed and complete and partial responses) and survival of patients treated with this regimen.
Determine the toxicity of this regimen in these patients.
Correlate chromosomal breakpoints, translocated immunoglobulin regulatory sequences, and cyclins D1, D2, and D3 with response and progression-free survival in patients treated with this regimen.
Correlate gene expression (measured by DNA microarray analysis) with response and progression-free survival in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

Courses 1, 3, 5, and 7: Patients receive rituximab IV on day 1 (courses 1, 3, and 5 only); cyclophosphamide IV over 3 hours twice a day on days 2-4; doxorubicin IV over 24 hours on days 5-7; vincristine IV on days 5 and 12; dexamethasone orally or IV four times a day on days 2-5 and 12-15; and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 8 and continuing until blood counts recover.
Courses 2, 4, 6, and 8: Patients receive rituximab IV on day 1 (courses 2, 4, and 6 only); high-dose methotrexate IV over 24 hours on day 2; high-dose cytarabine IV over 2 hours twice a day on days 3-4; oral leucovorin calcium 4 times a day on days 3-10; and G-CSF SC daily beginning on day 5 and continuing until blood counts recover.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed within 30 days, every 3 months for 2 years, and then every 6 months for 3 years. Patients with disease progression are followed annually for up to 5 years from study entry.

PROJECTED ACCRUAL: Approximately 50 patients will be accrued for this study within 25 months.

Eligibility

Ages Eligible for Study:	18 Years to 69 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically proven stage III/IV or bulky stage II mantle cell lymphoma of one of the following histologic subtypes:
- Nodular
- Diffuse
- Mantle zone
- Blastic
Newly diagnosed and previously untreated disease
Bidimensionally measurable disease

PATIENT CHARACTERISTICS:

Age:

18 to 69

Performance status:

Zubrod 0-2

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count at least 1,000/mm^3
Platelet count at least 100,000/mm^3 (50,000/mm^3 if marrow involvement present)

Hepatic:

Bilirubin no greater than 1.5 mg/dL (5.0 mg/dL if hepatic involvement present)

Renal:

Creatinine no greater than 2.0 mg/dL
Creatinine clearance greater than 50 mL/min

Cardiovascular:

Ejection fraction at least 50% by MUGA or 2-D echocardiogram
No significant abnormalities by EKG

Other:

Not pregnant or nursing
Fertile patients must use effective contraception
Willing to receive blood product transfusions
No known sensitivity to E. coli-derived proteins
No known AIDS syndrome or HIV-associated complex
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior monoclonal antibody therapy

Chemotherapy:

No prior chemotherapy for lymphoma

Endocrine therapy:

Not specified

Radiotherapy:

No prior radiotherapy for lymphoma

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00041132

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Elliot M. Epner, MD, PhD

OHSU Knight Cancer Institute

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:	Southwest Oncology Group
ClinicalTrials.gov Identifier:	NCT00041132 History of Changes
Other Study ID Numbers:	CDR0000069445, U10CA032102, S0213
Study First Received:	July 8, 2002
Results First Received:	March 5, 2012
Last Updated:	October 3, 2012
Health Authority:	United States: Federal Government

Keywords provided by Southwest Oncology Group:

stage III mantle cell lymphoma
stage IV mantle cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II 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
Cyclophosphamide
Cytarabine
Methotrexate
Rituximab
Dexamethasone
Doxorubicin

Vincristine
Lenograstim
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Leucovorin
Levoleucovorin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on May 16, 2013