A Phase I Trial of a Combined Regimen of Chemotherapy and 90Y-Labeled, Humanized LL2 (Anti-CD22) Antibody With Peripheral Stem Cell Rescue for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma
OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of yttrium Y
90 humanized anti-CD22 LL2 (Y90 MOAB hLL2) in combination with salvage chemotherapy and
autologous peripheral blood stem cell rescue in patients with recurrent or refractory B-cell
malignancies. II. Study the effect of chemotherapy on the uptake of Y90 MOAB hLL2 into tumor
sites and normal organs by pretherapy imaging using indium In 111 humanized LL2 and
intratherapy imaging. III. Determine the extent and duration of tumor response in patients
receiving this regimen.
OUTLINE: This is a dose escalation study of yttrium Y 90 humanized anti-CD22 monoclonal
antibody LL2 (Y90 MOAB hLL2). Patients receive filgrastim (G-CSF) subcutaneously daily for 5
days and undergo harvest of peripheral blood stem cells (PBSC) on 2 or more consecutive
days. If an adequate number of CD34+ cells are not harvested, autologous bone marrow may be
used. Chemotherapy-induced mobilization with filgrastim allowed. Patients undergo pretherapy
imaging with indium In 111 humanized LL2 (In111 hLL2) for up to 40 minutes on day -7.
Patients receive Y90 MOAB hLL2 for up to 40 minutes on day 0 plus In111 hLL2, followed by
Y90 MOAB hLL2 alone on day 3. Patients receive ifosfamide IV over 1 hour, cisplatin IV over
2 hours, and cytarabine IV over 2 hours on days 1 and 4. Oral etoposide is given daily on
days 1-7. PBSC or bone marrow is reinfused on days 9-14, depending on MOAB clearance.
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 3 or 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: Approximately 15-24 patients will be accrued for this study within 2-2.5
Primary Purpose: Treatment
Jack D. Burton, MD
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
United States: Federal Government
|Garden State Cancer Center||Belleville, New Jersey 07103|