Chemotherapy and Rituximab With or Without Total-Body Irradiation and Peripheral Stem Cell Transplant in Treating Patients With Lymphoma

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Genentech
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00039195
First received: June 6, 2002
Last updated: April 26, 2013
Last verified: April 2013
  Purpose

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 chemotherapy with monoclonal antibody therapy, total-body irradiation, and peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving chemotherapy with rituximab followed by combination chemotherapy with or without rituximab, total-body irradiation, and peripheral stem cell transplant works in treating patients with lymphoma.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: carboplatin
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Drug: prednisone
Drug: vincristine sulfate
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Risk-Adapted Therapy for Patients With Untreated Age-Adjusted International Prognostic Index II or III Diffuse Large B Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Complete remission rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 98
Study Start Date: November 2006
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen A consolidation chemotherapy
Patients receive consolidation chemotherapy comprising etoposide IV over 1 hour on days 1-3, ifosfamide IV continuously over 24 hours on day 2, carboplatin IV on day 2, and G-CSF SC once daily on days 5-12 or PEG-filgrastim once at least 24 hours after infusion. Treatment repeats every 14 days for a total of 3 courses in the absence of disease progression or unacceptable toxicity.
Biological: filgrastim Biological: rituximab Drug: carboplatin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: prednisone Drug: vincristine sulfate
Experimental: Regimen B
Patients receive consolidation chemotherapy as in regimen A for 3 courses. Patients also receive rituximab IV on days -3 to -1 of course 3 of chemotherapy. Patients undergo leukapheresis at the completion of course 3 (G-CSF continues from day 5 until the end of leukapheresis). After completion of leukapheresis, patients begin a regimen of high-dose chemoradiotherapy comprising either total body irradiation twice daily on days -10 to -7 and ifosfamide IV over 1 hour and etoposide IV continuously on days -6 to -2 or BEAM chemotherapy comprising carmustine, etoposide, cytarabine, and melphalan. Autologous peripheral blood stem cells (APBSC) are reinfused on day 0. Patients also receive G-CSF SC daily beginning on day 5 and continuing until blood counts recover. Beginning on day 42 post-APBSC, if blood counts have recovered, patients receive rituximab IV once weekly for 4 weeks. Rituximab is repeated beginning on day 180 in the absence of disease progression.
Biological: filgrastim Biological: rituximab Drug: carboplatin Drug: etoposide Drug: ifosfamide Drug: prednisone Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

  • Determine the complete remission rate in patients with low-intermediate-, high-intermediate-, or high-risk, CD20-positive, diffuse large B-cell lymphoma treated with induction chemotherapy and rituximab followed by consolidation chemotherapy with or without rituximab, total body irradiation, and autologous peripheral blood stem cell transplantation.
  • Evaluate positron emission tomography imaging for risk stratification of aggressive lymphoma by biopsy confirmation of residual lesions at interim restaging in patients treated with these regimens.
  • Determine the safety and toxicity of these regimens in these patients.

OUTLINE: Patients are stratified according to risk (low-intermediate vs high-intermediate or high).

Patients receive induction chemotherapy comprising cyclophosphamide IV, doxorubicin IV over 15 minutes, and vincristine IV over 1-2 minutes on day 1; oral prednisone once daily on days 1-5; and filgrastim (G-CSF) subcutaneously (SC) once daily on days 7-11 or PEG-filgrastim once at least 24 hours after infusion. Patients also receive rituximab IV 2-3 days apart for a total of 2 doses during the week prior to the first course of chemotherapy and on day 1 of courses 2-4 of chemotherapy. Treatment repeats every 14 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.

After the completion of induction chemotherapy, patients undergo CT scan and positron emission tomography (PET) scanning. If the PET scan is positive in one or more nodal sites, a repeat biopsy is performed. Patients with a negative PET scan OR a negative repeat biopsy (including no evidence of lymphoma on repeat bone marrow biopsy) are assigned to receive regimen A for consolidation therapy. Patients with a positive repeat biopsy are assigned to receive regimen B for consolidation therapy.

  • Regimen A: Patients receive consolidation chemotherapy comprising etoposide IV over 1 hour on days 1-3, ifosfamide IV continuously over 24 hours on day 2, carboplatin IV on day 2, and G-CSF SC once daily on days 5-12 or PEG-filgrastim once at least 24 hours after infusion. Treatment repeats every 14 days for a total of 3 courses in the absence of disease progression or unacceptable toxicity.
  • Regimen B: Patients receive consolidation chemotherapy as in regimen A for 3 courses. Patients also receive rituximab IV on days -3 to -1 of course 3 of chemotherapy. Patients undergo leukapheresis at the completion of course 3 (G-CSF continues from day 5 until the end of leukapheresis). After completion of leukapheresis, patients begin a regimen of high-dose chemoradiotherapy comprising either total body irradiation twice daily on days -10 to -7 and ifosfamide IV over 1 hour and etoposide IV continuously on days -6 to -2 or BEAM chemotherapy comprising carmustine, etoposide, cytarabine, and melphalan. Autologous peripheral blood stem cells (APBSC) are reinfused on day 0. Patients also receive G-CSF SC daily beginning on day 5 and continuing until blood counts recover. Beginning on day 42 post-APBSC, if blood counts have recovered, patients receive rituximab IV once weekly for 4 weeks. Rituximab is repeated beginning on day 180 in the absence of disease progression.

Patients who receive consolidation therapy on regimen A are followed at 4-6 weeks after chemotherapy and patients who receive consolidation therapy on regimen B are followed at 90-120 days after transplantation. All patients are followed closely for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 40-98 patients will be accrued for this study within 4 years.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed aggressive diffuse large B-cell lymphoma
  • CD20-positive disease
  • Age-adjusted International Prognostic Index II or III defined by the presence of at least 1 of the following:

    • Karnofsky performance status 10-70%
    • Lactate dehydrogenase greater than 200 U/L
    • Stage III or IV disease
  • Positron emission tomography avid measurable disease
  • No CNS involvement

PATIENT CHARACTERISTICS:

Age:

  • 18 to 64

Performance status:

  • See Disease Characteristics

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count greater than 1,000/mm^3
  • Platelet count greater than 50,000/mm^3

Hepatic:

  • Bilirubin less than 2.0 mg/dL unless history of Gilbert's disease or pattern consistent with Gilbert's disease
  • Hepatitis B surface antigen and hepatitis C antibody negative
  • No chronic, active, or persistent hepatitis

Renal:

  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance greater than 60 mL/min
  • No chronic renal insufficiency

Cardiovascular:

  • Ejection fraction at least 50% by echocardiogram or MUGA scan
  • No myocardial infarction within the past 6 months
  • No unstable angina
  • No cardiac arrhythmias except chronic atrial fibrillation

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception
  • HIV negative
  • No other medical illness that would preclude study
  • No uncontrolled infection
  • No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior biologic therapy for malignancy

Chemotherapy:

  • No prior chemotherapy for malignancy

Endocrine therapy:

  • Prior steroids allowed if received no more than 1 week of therapy

Radiotherapy:

  • No prior radiotherapy for malignancy

Surgery:

  • No prior surgery for malignancy

Other:

  • No other prior therapy for malignancy
  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: NCT00039195

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Bristol-Myers Squibb
Genentech
Investigators
Study Chair: Craig Moskowitz, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00039195     History of Changes
Other Study ID Numbers: 01-142, MSKCC-01142, NCI-G02-2069
Study First Received: June 6, 2002
Last Updated: April 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
stage I adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Rituximab
Etoposide phosphate
Liposomal doxorubicin
Isophosphamide mustard
Carboplatin
Cyclophosphamide
Doxorubicin
Etoposide
Vincristine
Ifosfamide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014