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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00242996
First received: October 20, 2005
Last updated: March 20, 2014
Last verified: March 2014
  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 2

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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

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
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Lode J. Swinnen, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00242996     History of Changes
Other Study ID Numbers: CDR0000447158 J0376, P30CA006973, JHOC-J0376, WIRB-20040009
Study First Received: October 20, 2005
Last Updated: March 20, 2014
Health Authority: United States: Federal Government

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
recurrent adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Rituximab
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014