Clinical trial NCT00006695: Monoclonal Antibody Therapy, Combination Chemotherapy, and Peripheral Stem Cell Transplant in Non-Hodgkin's Lymphoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2003-01-27
Enrollment: 50
Sex: ALL
Minimum age (years): 19
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Event free survival rate
timeFrame: 100 days post transplant and at yearly intervals
Secondary outcomes:
measure: Time to treatment failure
timeFrame: time of registration to time of treatment discontinuation or withdrawal for progression
measure: Overall survival
timeFrame: Time from registration to last participant death
Other outcomes:
Locations:
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Julie M. Vose, MD
role: STUDY_CHAIR
References: