S0213 Chemotherapy Plus Rituximab in Treating Patients With Mantle Cell Lymphoma

October 3, 2012 updated by: Southwest Oncology Group

Pilot Trial of Hyper-CVAD and Methotrexate/ARA C Plus Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • cytoxan
Drug: cytarabine
12 g/m^2 over days 3-4 of cycles 2,4,6,8
Other Names:
  • 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 Names:
  • adriamycin
Drug: leucovorin
170 mg over days 3-5 of cycles 2,4,6,8
Other Names:
  • leucovorin calcium
Drug: methotrexate
1000 mg/m^2 over days 2-3 of cycles 2,4,6,8
Other Names:
  • MTX
Drug: vincristine
1.4 mg/m^2 on days 5 and 12 of cycles 1,3,5,7
Other Names:
  • vincristine sulfate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival
Time Frame: assessed after cycle 4, after completion of treatment, then every 3 months until 1 year after registration
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.
assessed after cycle 4, after completion of treatment, then every 3 months until 1 year after registration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response
Time Frame: assessed after cycle 4 and after completion of treatment (168 days)
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.
assessed after cycle 4 and after completion of treatment (168 days)
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
Overall Survival rate at 1 year. Time to death is from date of registration to date of death due to any cause.
assessed after cycle 4, after completion of treatment, then every 3 months for 2 years, then every 6 months thereafter until 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southwest Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Elliot M. Epner, MD, PhD, OHSU Knight Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • 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).

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2002

Primary Completion (Actual)

November 1, 2007

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

July 8, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

November 1, 2012

Last Update Submitted That Met QC Criteria

October 3, 2012

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000069445
  • U10CA032102 (U.S. NIH Grant/Contract)
  • S0213 (Other Identifier: SWOG)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma

Clinical Trials on filgrastim

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Sweden

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe