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

NCT ID: NCT00039195

Last Updated: 2016-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2010-01-31

Brief Summary

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.

Detailed Description

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Induction R-CHOPac Therapy for patients with B-Cell Lymphoma

Patients received 4 cycles if accelerated R-CHOP (cyclophosphamide. doxorubicin, vincristine and prednisone + rituximab) followed by 3 cycles ICE (ifosfamide, carboplatin and etoposide) consolidation therapy.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Interventions

filgrastim

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Craig Moskowitz, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

References

Bantilan KS, Smith AN, Maurer MJ, Teruya-Feldstein J, Matasar MJ, Moskowitz AJ, Straus DJ, Noy A, Palomba ML, Horwitz SM, Hamlin PA, Portlock CS, Cerhan JR, Habermann TM, Salles GA, Nowakowski GS, Moskowitz CH, Zelenetz AD. Matched control analysis suggests that R-CHOP followed by (R)-ICE may improve outcome in non-GCB DLBCL compared with R-CHOP. Blood Adv. 2024 May 14;8(9):2172-2181. doi: 10.1182/bloodadvances.2023011408.

Reference Type: DERIVED

PMID: 38271621 (View on PubMed)

Other Identifiers

MSKCC-01142

Identifier Type: -

Identifier Source: secondary_id

NCI-G02-2069

Identifier Type: -

Identifier Source: secondary_id

01-142

Identifier Type: -

Identifier Source: org_study_id