S0213 Chemotherapy Plus Rituximab in Treating Patients With Mantle Cell Lymphoma

NCT ID: NCT00041132

Last Updated: 2012-11-01

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-09-30

Study Completion Date

2011-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Lymphoma

Keywords

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stage III mantle cell lymphoma stage IV mantle cell lymphoma contiguous stage II mantle cell lymphoma noncontiguous stage II mantle cell lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

5 ug/kg

rituximab

Intervention Type BIOLOGICAL

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

cyclophosphamide

Intervention Type DRUG

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

cytarabine

Intervention Type DRUG

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

dexamethasone

Intervention Type DRUG

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

doxorubicin

Intervention Type DRUG

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

leucovorin

Intervention Type DRUG

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

methotrexate

Intervention Type DRUG

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

vincristine

Intervention Type DRUG

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

Interventions

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filgrastim

5 ug/kg

Intervention Type BIOLOGICAL

rituximab

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

Intervention Type BIOLOGICAL

cyclophosphamide

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

Intervention Type DRUG

cytarabine

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

Intervention Type DRUG

dexamethasone

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

Intervention Type DRUG

doxorubicin

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

Intervention Type DRUG

leucovorin

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

Intervention Type DRUG

methotrexate

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

Intervention Type DRUG

vincristine

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

Intervention Type DRUG

Other Intervention Names

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G-CSF cytoxan Ara-C adriamycin leucovorin calcium MTX vincristine sulfate

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elliot M. Epner, MD, PhD

Role: STUDY_CHAIR

OHSU Knight Cancer Institute

Countries

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United States

References

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A multi center trial of hyperCVAD+rituxan in patients with newly diagnosed mantle cell lymphoma EM Epner; J Unger; T Miller; L Rimsza; C Spier; M LeBlanc; R Fisher. Blood 110(11):#387. (2007).

Reference Type RESULT

Other Identifiers

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U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

S0213

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000069445

Identifier Type: -

Identifier Source: org_study_id