Monoclonal Antibody Therapy, Combination Chemotherapy, and Peripheral Stem Cell Transplant in Non-Hodgkin's Lymphoma

University of Nebraska

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Drug: melphalan

Radiation: tositumomab and iodine I 131 tositumomab

Drug: etoposide

Procedure: peripheral blood stem cell transplantation

Drug: cytarabine

Drug: carmustine

Study type

Interventional

Funder types

Other

Identifiers

NCT00006695

0051-00-FB

COULTER-IND-3323

Details and patient eligibility

About

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.

Full 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.

Enrollment

50 patients

Sex

All

Ages

19 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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
Adequate peripheral blood stem cells
- At least 15,000,000 CD34+ cells/kg or
- At least 25,000 granulocyte macrophage colony-forming units/kg
Age: 19 to 70
Performance status: Karnofsky 70-100%
Life expectancy: at least 4 months post-transplantation
Bilirubin less than 2.0 mg/dL
Creatinine less than 2.0 mg/dL
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
DLCO at least 50% of predicted
HIV negative
Fertile patients must use effective contraception during and for at least 6 months after study participation
At least 4 weeks since prior biologic therapy and recovered
Human antimouse antibody negative
At least 4 weeks since prior cytotoxic chemotherapy and recovered
At least 4 weeks since prior radiotherapy and recovered
At least 4 weeks since prior immunosuppressants and recovered

Exclusion criteria

No progressive disease in a field that has been previously irradiated with more than 3,500 cGy within the past year
No known brain or leptomeningeal metastases
No active obstructive hydronephrosis
No New York Heart Association class III or IV heart disease
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
Not pregnant/negative pregnancy test
No prior peripheral blood stem cell transplantation following high-dose chemotherapy or chemoradiotherapy
No other concurrent biologic therapy for NHL
No concurrent steroids except maintenance-dose steroids for noncancerous disease
No concurrent external beam radiotherapy for NHL
No other concurrent participation on protocol involving non-FDA-approved drugs or biologics