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

June 29, 2016 updated by: Memorial Sloan Kettering Cancer Center

Risk-Adapted Therapy for Patients With Untreated Age-Adjusted International Prognostic Index II or III Diffuse Large B Cell Lymphoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

98

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: carboplatin
Drug: cyclophosphamide
Radiation: radiation therapy
Drug: prednisone
Drug: etoposide
Drug: vincristine sulfate
Drug: doxorubicin hydrochloride
Procedure: peripheral blood stem cell transplantation
Biological: filgrastim
Biological: rituximab
Drug: ifosfamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 2 years
Kaplan-Meier estimates will be used to verify the progression free survival.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Bristol-Myers Squibb
National Cancer Institute (NCI)
Genentech, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

June 6, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

August 10, 2016

Last Update Submitted That Met QC Criteria

June 29, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01-142
  • MSKCC-01142
  • NCI-G02-2069

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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