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S0349 Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Oblimersen in Treating Patients With Advanced Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Primary Purpose

Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
oblimersen sodium
rituximab
cyclophosphamide
doxorubicin hydrochloride
vincristine sulfate
prednisone
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Contiguous Stage II Adult Diffuse Large Cell Lymphoma

Eligibility Criteria

19 Years - 59 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: All patients must have previously untreated stage III, IV, or bulky stage II diffuse large B-cell non-Hodgkin's lymphoma which is positive for CD20 Adequate sections from the original diagnostic specimen must be available for submission for review; an adequate biopsy requires sufficient tissue to establish the architecture and a REAL or WHO histologic subtype with certainty; thus, core biopsies, especially multiple core biopsies MAY be adequate; whereas, needle aspirations or cytologies are not adequate Patients may also be registered to SWOG-8947 and SWOG-8819 Patients must have an age-adjusted International Prognostic Index score of 0 or 1 All patients must have bidimensionally measurable disease documented within 28 days prior to registration; patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration Patients must have a unilateral bone marrow aspirate and biopsy performed within 42 days prior to registration Patients must have a CT scan of the chest and abdomen/pelvis performed within 28 days prior to registration Patients must not have clinical evidence of central nervous system involvement by lymphoma; any laboratory or radiographic tests performed to assess CNS involvement must be negative within 42 days of registration Patients must not have a previous diagnosis of indolent lymphoma (histologic transformation are ineligible); as patients with nodal diffuse large ell lymphoma may have bone marrow involvement with small lymphocytes, such patients are eligible Patients must not have received prior chemotherapy, radiation, or antibody therapy for lymphoma All patients must have a Zubrod performance status of 0-2 Serum LDH must be measured within 28 days prior to registration Patients must have a cardiac ejection fraction >= 45% by MUGA scan or an ECHO with no significant abnormalities within 42 days prior to registration Patients known to be HIV positive, or who have a history of solid organ transplantation are ineligible as the biology and natural history of HIV associated, or post transplant lymphomas are very different than that of de novo diffuse large cell lymphomas; patients at high risk of hepatitis B virus infection should be screened before initiation of rituximab Patients requiring continuing supplemental oxygen therapy are ineligible No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years Pregnant or nursing women may not participate due to the potential for congenital abnormalities, and of harm to nursing infants due to this treatment regimen; women or men of reproductive potential may no participate unless they have agreed to use an effective contraceptive method If day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day In calculating days of tests and measurements, the day a test or measurement is done is considered day 0; therefore, if a test is done on a Monday, the Monday 4 weeks later would be considered day 28; this allows for efficient patient scheduling without exceeding the guidelines All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base

Sites / Locations

  • Southwest Oncology Group

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (closed to accrual as of 9/21/04)

Arm II

Arm Description

Patients receive rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5.

Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10.

Outcomes

Primary Outcome Measures

1 year PFS

Secondary Outcome Measures

Overall survival
Response
1-year PFS in patients who are bcl2+
Overall survival in patients who are bcl2+
Response in patients who are bcl2+

Full Information

First Posted
April 7, 2004
Last Updated
January 4, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00080847
Brief Title
S0349 Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Oblimersen in Treating Patients With Advanced Diffuse Large B-Cell Non-Hodgkin's Lymphoma
Official Title
Standard Dose Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) and Rituximab, or Rituximab and G3139 Phosphorothioate Oligonucleotide (BCL-2 Antisense - NSC-683428) Therapy for Young Patients (< Age 60) With Advanced Stage Diffuse Large B-Cell NHL of Low and Low-Intermediate IPI Risk
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Terminated
Study Start Date
March 2004 (undefined)
Primary Completion Date
June 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This randomized phase II trial is studying rituximab and combination chemotherapy to see how well they work compared to oblimersen, rituximab, and combination chemotherapy in treating patients with advanced diffuse large B-cell non-Hodgkin's lymphoma. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of anticancer drugs by making cancer cells more sensitive to the drugs. Combining rituximab and combination chemotherapy with oblimersen may kill more cancer cells
Detailed Description
PRIMARY OBJECTIVES: I. To estimate the 1-year progression-free survival probability rate in younger patients with low and low-intermediate IPI risk advanced stage diffuse large B-cell NHL treated with 8-cycles of CHOP-rituximab. (The CHOP-rituximab arm of this study was permanently closed, effective 10/15/04.) II. To estimate the 1-year progression-free survival probability rate in younger patients with low and low-intermediate IPI risk advanced stage diffuse large B-cell NHL treated with 8 cycles of CHOP-rituximab-G3139. III. To evaluate response (complete, complete unconfirmed, and partial) and toxicity for these regimens in this patient population. (The CHOP-rituximab arm of this study was permanently closed, effective 10/15/04.) IV. To estimate the 1-year progression-free survival and response rate in the subset of patients overexpressing bcl-2 protein. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age-adjusted International Prognostic Index (0 vs 1). Patients are randomized to 1 of 2 treatment arms. (Arm I closed to accrual as of 9/21/04.) ARM I (closed to accrual as of 9/21/04): Patients receive rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5. ARM II: Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10. In both arms, treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for up to 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
160 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (closed to accrual as of 9/21/04)
Arm Type
Experimental
Arm Description
Patients receive rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5.
Arm Title
Arm II
Arm Type
Experimental
Arm Description
Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10.
Intervention Type
Biological
Intervention Name(s)
oblimersen sodium
Other Intervention Name(s)
augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Other Intervention Name(s)
ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Other Intervention Name(s)
leurocristine sulfate, VCR, Vincasar PFS
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
prednisone
Other Intervention Name(s)
DeCortin, Deltra
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
1 year PFS
Time Frame
At 1 year
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
Up to 7 years
Title
Response
Time Frame
Up to 7 years
Title
1-year PFS in patients who are bcl2+
Time Frame
At 1 year
Title
Overall survival in patients who are bcl2+
Time Frame
Up to 7 years
Title
Response in patients who are bcl2+
Time Frame
Up to 7 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients must have previously untreated stage III, IV, or bulky stage II diffuse large B-cell non-Hodgkin's lymphoma which is positive for CD20 Adequate sections from the original diagnostic specimen must be available for submission for review; an adequate biopsy requires sufficient tissue to establish the architecture and a REAL or WHO histologic subtype with certainty; thus, core biopsies, especially multiple core biopsies MAY be adequate; whereas, needle aspirations or cytologies are not adequate Patients may also be registered to SWOG-8947 and SWOG-8819 Patients must have an age-adjusted International Prognostic Index score of 0 or 1 All patients must have bidimensionally measurable disease documented within 28 days prior to registration; patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration Patients must have a unilateral bone marrow aspirate and biopsy performed within 42 days prior to registration Patients must have a CT scan of the chest and abdomen/pelvis performed within 28 days prior to registration Patients must not have clinical evidence of central nervous system involvement by lymphoma; any laboratory or radiographic tests performed to assess CNS involvement must be negative within 42 days of registration Patients must not have a previous diagnosis of indolent lymphoma (histologic transformation are ineligible); as patients with nodal diffuse large ell lymphoma may have bone marrow involvement with small lymphocytes, such patients are eligible Patients must not have received prior chemotherapy, radiation, or antibody therapy for lymphoma All patients must have a Zubrod performance status of 0-2 Serum LDH must be measured within 28 days prior to registration Patients must have a cardiac ejection fraction >= 45% by MUGA scan or an ECHO with no significant abnormalities within 42 days prior to registration Patients known to be HIV positive, or who have a history of solid organ transplantation are ineligible as the biology and natural history of HIV associated, or post transplant lymphomas are very different than that of de novo diffuse large cell lymphomas; patients at high risk of hepatitis B virus infection should be screened before initiation of rituximab Patients requiring continuing supplemental oxygen therapy are ineligible No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years Pregnant or nursing women may not participate due to the potential for congenital abnormalities, and of harm to nursing infants due to this treatment regimen; women or men of reproductive potential may no participate unless they have agreed to use an effective contraceptive method If day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day In calculating days of tests and measurements, the day a test or measurement is done is considered day 0; therefore, if a test is done on a Monday, the Monday 4 weeks later would be considered day 28; this allows for efficient patient scheduling without exceeding the guidelines All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Bernstein
Organizational Affiliation
SWOG Cancer Research Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southwest Oncology Group
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78245
Country
United States

12. IPD Sharing Statement

Learn more about this trial

S0349 Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Oblimersen in Treating Patients With Advanced Diffuse Large B-Cell Non-Hodgkin's Lymphoma

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