Phase I/II Radioimmunotherapy of Non-Hodgkin's Lymphoma With High-Dose 90Y-Labeled Humanized LL2 Anti-CD-22 Antibody and Peripheral Blood Stem Cell Rescue
OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of
radioimmunotherapy using high dose yttrium Y 90 humanized anti-CD22 monoclonal antibody LL2
(Y90 MOAB hLL2) followed by autologous peripheral blood stem cell transplantation in
patients with B cell lymphomas or Waldenstrom's macroglobulinemia. II. Determine the organ
and tumor dosimetry for comparison to clinical measurement of toxicity and antitumor
responses in these patients. III. Determine magnitude and duration of human anti-humanized
LL2 antibody (HAhLL2) or anti-DOTA response in these patients. IV. Evaluate the extent and
duration of antitumor response to this regimen in these patients.
OUTLINE: This is a dose escalation, multicenter study. Patients are stratified according to
prior treatment (high dose chemotherapy with transplantation vs low dose chemotherapy with
radioimmunotherapy (RAIT) vs low dose chemotherapy without RAIT). Patients receive
filgrastim (G-CSF) subcutaneously (SC) daily for 5 days and undergo harvest of peripheral
blood stem cells (PBSC). If an adequate number of CD34+ cells are not harvested, autologous
bone marrow may be used. Patients undergo pretherapy imaging with indium In 111 monoclonal
antibody MN-14 (In111-MN-14) IV on day -7. If at least 1 tumor site is targeted, patients
receive high dose yttrium Y 90 humanized anti-CD22 monoclonal antibody LL2 (Y90 MOAB hLL2)
IV for up to 50 minutes on day 0. PBSC or bone marrow is reinfused approximately 7-14 days
following infusion of Y90 MOAB hLL2. Patients also receive G-CSF SC daily until 3 days after
blood counts have recovered. Cohorts of 3-6 patients receive escalating doses of Y90 MOAB
hLL2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are
followed weekly for 2 months, monthly for 6 months, and then every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study within 2 years.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Jack D. Burton, MD
Study Chair
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
United States: Food and Drug Administration
CDR0000067327
NCT00004107
February 1998
Name | Location |
---|---|
University of Pennsylvania Cancer Center | Philadelphia, Pennsylvania 19104 |
St. Barnabas Medical Center | Livingston, New Jersey 07039 |
St. Joseph's Hospital and Medical Center | Paterson, New Jersey 07503 |
Garden State Cancer Center | Belleville, New Jersey 07103 |