Rituximab, Cyclophosphamide, and G-CSF Followed By Combination Chemotherapy in Treating Patients Who Are Undergoing Autologous Stem Cell Transplant Followed By Rituximab and GM-CSF for Refractory Diffuse Large B-Cell Lymphoma - Full Text View

Sponsors and Collaborators:	Sidney Kimmel Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00242996

Purpose

RATIONALE: Giving colony-stimulating factors, such as G-CSF, monoclonal antibodies, such as rituximab, and chemotherapy, such as cyclophosphamide, helps stem cells move from the patient's bone marrow to the blood so they can be collected and stored for peripheral stem cell transplant. Giving chemotherapy, such as carmustine, etoposide, and cyclophosphamide, before transplant stops the growth of cancer cells by stopping them from dividing or killing them. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. More rituximab is given after transplant to kill any remaining cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with cyclophosphamide and G-CSF followed by combination chemotherapy works in treating patients undergoing an autologous stem cell transplant followed by rituximab and GM-CSF for refractory diffuse large B-cell lymphoma.

Condition	Intervention	Phase
Lymphoma	Biological: filgrastim Biological: rituximab Biological: sargramostim Drug: carmustine Drug: cyclophosphamide Drug: etoposide Procedure: adjuvant therapy Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase II Trial of Rituximab and Autologous Stem Cell Transplantation for Refractory B Cell Large Cell Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Etoposide Granulocyte-macrophage colony-stimulating factor Filgrastim Sargramostim Rituximab Carmustine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

2-year event free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	44
Study Start Date:	March 2004

Detailed Description:

OBJECTIVES:

Determine the disease-free and overall survival of patients with refractory diffuse large B-cell lymphoma treated with stem cell mobilization comprising rituximab, cyclophosphamide, and filgrastim (G-CSF) followed by high-dose chemotherapy comprising carmustine, etoposide, and cyclophosphamide and autologous peripheral blood stem cell transplantation, rituximab, and sargramostim (GM-CSF).
Determine any potential infectious complications in patients treated with this regimen.
Determine the effect of GM-CSF on antibody-dependent cellular cytotoxicity in patients treated with this regimen.

OUTLINE: Stem cell mobilization: Patients receive rituximab IV over 4-8 hours on days 1, 5, 8, and 13. Patients also receive cyclophosphamide IV over 1-2 hours on day 9 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 10 and continuing until an adequate number of peripheral blood stem cells (PBSC) are collected.

High-dose preparative regimen: Patients receive carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2.

Autologous PBSC transplantation: Patients undergo autologous PBSC transplantation on day 0. Patients receive sargramostim (GM-CSF) SC once daily beginning on day 6 and continuing until blood counts recover.

Post-transplant regimen: Patients receive GM-CSF SC once daily on days 42-73, 177-208, 362-393, 543-574, and 727-758. Patients also receive rituximab IV over 4-8 hours on days 45, 52, 59, 66, 180,187, 194, 201, 365, 372, 379, 386, 546, 553, 560, 567, 730, 737, 744, and 751.

After completion of study treatment, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of diffuse large B-cell lymphoma, meeting 1 of the following criteria:
- Failed to achieve at least partial remission
- Failed to respond to prior primary therapy or salvage chemotherapy
- Disease progression within 6 weeks after achieving remission
CD20 expression at diagnosis or relapse
No more than 4 prior regimens using chemotherapy, radiotherapy, or immunotherapy
- The addition of radiotherapy or a monoclonal antibody to chemotherapy is considered 1 treatment regimen provided the addition was part of the initial treatment plan
  - The addition of these therapies due to lack of response or poor response is considered an additional treatment regimen whether given in the front line or salvage setting

PATIENT CHARACTERISTICS:

Performance status

ECOG 0-1

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,000/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Direct bilirubin ≤ 2 mg/dL
AST or ALT < 3 times upper limit of normal

Renal

Creatinine ≤ 2.0 mg/dL

Cardiovascular

Ejection fraction ≥ 40%

Pulmonary

DLCO ≥ 60% of predicted

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
No active infection requiring oral or IV antibiotics
HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
See Radiotherapy

Chemotherapy

See Disease Characteristics

Radiotherapy

See Disease Characteristics
No prior radioimmunotherapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00242996

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Lode J. Swinnen, MD

Sidney Kimmel 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

Study ID Numbers:	CDR0000447158, JHOC-J0376, WIRB-20040009
Study First Received:	October 20, 2005
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00242996 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult diffuse large cell lymphoma

Study placed in the following topic categories:

Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Immunologic Factors
Rituximab
Carmustine
Adjuvants, Immunologic
Cyclophosphamide
Immunosuppressive Agents
Etoposide phosphate
Recurrence
Lymphoma, B-Cell

Lymphatic Diseases
B-cell Lymphomas
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma, Large-cell
Alkylating Agents
Etoposide
Lymphoma

Additional relevant MeSH terms:

Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Rituximab
Physiological Effects of Drugs
Carmustine
Cyclophosphamide
Immunosuppressive Agents

Pharmacologic Actions
Lymphoma, B-Cell
Lymphatic Diseases
Neoplasms
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Alkylating Agents
Lymphoma

ClinicalTrials.gov processed this record on September 10, 2009