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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT00006695
First received: December 6, 2000
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • event free survival rate [ Time Frame: 100 days post transpat and at yearly intervals ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • time to treatment failure [ Time Frame: time of registration to time of treatment discotinuation or withdrawal for progression ] [ Designated as safety issue: No ]
  • over all survival [ Time Frame: when all treated patients have expired ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: April 2000
Estimated Study Completion Date: January 2015
Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Iodine-131 Anti-B1 Antibody

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

Ages Eligible for Study:   19 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006695

Locations
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
Sponsors and Collaborators
University of Nebraska
Investigators
Study Chair: Julie M. Vose, MD University of Nebraska
  More Information

Additional Information:
No publications provided

Responsible Party: Julie M Vose, MD, Professor & N/M Harris Oncology Professorship, University of Nebraska
ClinicalTrials.gov Identifier: NCT00006695     History of Changes
Other Study ID Numbers: 051-00, UNMC-051-00, COULTER-IND-3323
Study First Received: December 6, 2000
Last Updated: April 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Nebraska:
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies
Antibodies, Monoclonal
Cadexomer iodine
Immunoglobulins
Iodine
Iodine-131 anti-B1 antibody
Anti-Infective Agents
Anti-Infective Agents, Local
Antineoplastic Agents
Growth Substances
Immunologic Factors
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Trace Elements

ClinicalTrials.gov processed this record on October 21, 2014