Monoclonal Antibody Therapy, Combination Chemotherapy, and Peripheral Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Sponsor

University of Nebraska (Other)

Overall Status

Completed

CT.gov ID

NCT00006695

Collaborator

(none)

Enrollment

Location

Arm

176

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with 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 monoclonal antibody therapy, chemotherapy, and peripheral stem cell transplant work in treating patients with relapsed or refractory non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: carmustine Drug: cytarabine Drug: etoposide Drug: melphalan Procedure: peripheral blood stem cell transplantation Radiation: tositumomab and iodine I 131 tositumomab	Phase 2

Detailed Description

OBJECTIVES:

Compare the response rates and time to treatment failure in patients with relapsed or refractory non-Hodgkin's lymphoma treated with iodine I 131 monoclonal antibody anti-B1, followed by high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM), and autologous peripheral blood stem cell transplantation (APBSCT) vs historical control patients treated with high-dose BEAM or carmustine, etoposide, cytarabine, and cyclophosphamide and APBSCT.
Determine the safety of this regimen in these patients.

OUTLINE: Autologous peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells or granulocyte macrophage colony-forming units. On day -19, patients receive unlabeled monoclonal antibody anti-B1 (MOAB anti-B1) IV followed by a dosimetric dose of iodine I 131 MOAB anti-B1 IV over 20 minutes. On day -12, patients receive unlabeled MOAB anti-B1 IV followed by a therapeutic dose of iodine I 131 MOAB anti-B1 IV over 20 minutes. Patients then receive high-dose chemotherapy comprising carmustine IV on day -6, etoposide IV and cytarabine IV twice daily on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous PBSC transplantation on day 0.

Patients are followed at days 30 and 100, at 6 months, and then annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study over 5 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

BEAM Plus Iodine-131 Anti-B1 Antibody and Autologous Hematopoietic Stem Cell Transplantation for Treatment of Recurrent Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Study Start Date :

Apr 1, 2000

Actual Primary Completion Date :

Sep 1, 2005

Actual Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Iodine-131 Anti-B1 Antibody/BEAM/autologous hematopoietic stem cell transplantation (AHSCT)	Drug: carmustine 300 mg/m2 IV on Day -6 Other Names: BCNU Drug: cytarabine 100 mg/m2 BID on Days -5 through -2 Drug: etoposide 100 mg/m2 BID on Days -5 through -2 Drug: melphalan 140 mg/m2 IV on Day -1 Procedure: peripheral blood stem cell transplantation Following the chemotherapy, on Day 0 of treatment, the previously stored hematopoietic stem cells will be administered to the patient intravenously through a central line to the patient. Other Names: Autologous Hematopoietic Stem Cell Transplantation Radiation: tositumomab and iodine I 131 tositumomab Patients will receive two administrations of Iodine-131 Anti-B1 Antibody; the "dosimetric dose" and the "therapeutic dose". The dosimetric dose will consist of an infusion of unlabeled Anti-B1 Antibody (450 mg) immediately followed by an infusion of Anti-B1 Antibody (35 mg) which has been trace labeled with 5 mCi of Iodine-131 Anti-B1 Antibody. Using whole body anterior and posterior gamma camera scans and serial imaging studies over approximately one week, the clearance of the whole body dosimetric dose will be used to calculate the subsequent therapeutic dose of Iodine-131 Anti-B1 Antibody which delivers a total body dose of 75 cGy to the subject Other Names: Iodine-131 Anti-B1 Antibody

Arm

Intervention/Treatment

Experimental: Arm I

Iodine-131 Anti-B1 Antibody/BEAM/autologous hematopoietic stem cell transplantation (AHSCT)

Drug: carmustine

300 mg/m2 IV on Day -6

Other Names:

BCNU

Drug: cytarabine

100 mg/m2 BID on Days -5 through -2

Drug: etoposide

100 mg/m2 BID on Days -5 through -2

Drug: melphalan

140 mg/m2 IV on Day -1

Procedure: peripheral blood stem cell transplantation

Following the chemotherapy, on Day 0 of treatment, the previously stored hematopoietic stem cells will be administered to the patient intravenously through a central line to the patient.

Other Names:

Autologous Hematopoietic Stem Cell Transplantation

Radiation: tositumomab and iodine I 131 tositumomab

Patients will receive two administrations of Iodine-131 Anti-B1 Antibody; the "dosimetric dose" and the "therapeutic dose". The dosimetric dose will consist of an infusion of unlabeled Anti-B1 Antibody (450 mg) immediately followed by an infusion of Anti-B1 Antibody (35 mg) which has been trace labeled with 5 mCi of Iodine-131 Anti-B1 Antibody. Using whole body anterior and posterior gamma camera scans and serial imaging studies over approximately one week, the clearance of the whole body dosimetric dose will be used to calculate the subsequent therapeutic dose of Iodine-131 Anti-B1 Antibody which delivers a total body dose of 75 cGy to the subject

Other Names:

Iodine-131 Anti-B1 Antibody

Outcome Measures

Primary Outcome Measures

event free survival rate [100 days post transpat and at yearly intervals]

Secondary Outcome Measures

time to treatment failure [time of registration to time of treatment discotinuation or withdrawal for progression]
over all survival [when all treated patients have expired]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of non-Hodgkin's lymphoma (NHL) of one of the following types:
Diffuse large B-cell
Composite (at least 50% of tumor showing diffuse histology)
Diffuse mixed cell
Immunoblastic
Relapsed or refractory disease sensitive to initial or subsequent conventional therapy (at least a partial response)
Eligible for high-dose carmustine, etoposide, cytarabine, and melphalan protocol and autologous bone marrow transplantation or peripheral blood stem cell transplantation
Evidence of CD20 antigen expression in tumor tissue
Bidimensionally measurable disease
No progressive disease in a field that has been previously irradiated with more than 3,500 cGy within the past year
Adequate peripheral blood stem cells
At least 15,000,000 CD34+ cells/kg OR
At least 25,000 granulocyte macrophage colony-forming units/kg
No known brain or leptomeningeal metastases

PATIENT CHARACTERISTICS:

Age:

19 to 70

Performance status:

Karnofsky 70-100%

Life expectancy:

At least 4 months posttransplantation

Hematopoietic:

See Disease Characteristics

Hepatic:

Bilirubin less than 2.0 mg/dL

Renal:

Creatinine less than 2.0 mg/dL
No active obstructive hydronephrosis

Cardiovascular:

Cardiac ejection fraction at least 40% for any of the following criteria:
Age 60 and over
Significant cardiac history (myocardial infarction or congestive heart failure)
Received greater than 350 mg/m^2 of prior doxorubicin
No New York Heart Association class III or IV heart disease

Pulmonary:

DLCO at least 50% of predicted

Other:

No evidence of severe organ dysfunction
No other major medical illnesses
No active infection requiring IV antibiotics
No other malignancy within the past 5 years except adequately treated skin cancer or carcinoma in situ of the cervix
HIV negative
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 6 months after study participation
Human antimouse antibody negative
No vulnerability

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics
No prior peripheral blood stem cell transplantation following high-dose chemotherapy or chemoradiotherapy
At least 4 weeks since prior biologic therapy and recovered
No other concurrent biologic therapy for NHL

Chemotherapy:

See Disease Characteristics
See Biologic therapy
At least 4 weeks since prior cytotoxic chemotherapy and recovered
No other concurrent chemotherapy or antineoplastic therapy for NHL

Endocrine therapy:

No concurrent steroids except maintenance-dose steroids for noncancerous disease

Radiotherapy:

See Disease Characteristics
See Biologic therapy
At least 4 weeks since prior radiotherapy and recovered
No concurrent external beam radiotherapy for NHL

Surgery:

Not specified

Other:

At least 4 weeks since prior immunosuppressants and recovered
No other concurrent participation on protocol involving non-FDA-approved drugs or biologics