Trial Information

A Phase I Study of 90Y-DOTA-Peptide-Lym-1 With Peripheral Blood Stem Cell Support, Paclitaxel And Cyclosporin A In Patients With Non-Hodgkin's Lymphoma

OBJECTIVES:

- Determine the maximum tolerated dose of yttrium Y 90 monoclonal antibody Lym-1
administered with cyclosporine and paclitaxel followed by autologous peripheral blood
stem cell transplantation in patients with refractory non-Hodgkin's lymphoma.

- Determine the toxicity of this treatment regimen in these patients.

OUTLINE: This is an open-label, dose escalation study of yttrium Y 90 monoclonal antibody
Lym-1 (Y90 MOAB Lym-1). Patients are assigned to one of four cohorts.

- Cohort I: Patients receive filgrastim (G-CSF) subcutaneously (SC) beginning 4 days
prior to peripheral blood stem cell (PBSC) mobilization and continuing until adequate
PBSC are collected. Patients receive unlabeled monoclonal antibody (MOAB) Lym-1 IV
followed by a tracer dose of indium In 111 MOAB Lym-1 (In111 MOAB Lym-1) IV on day 0
and unlabeled MOAB Lym-1 IV followed by Y90 MOAB Lym-1 IV on day 7. Patients also
receive oral cyclosporine every 12 hours on days -2 to 14. Patients may undergo
autologous PBSC transplantation, if necessary, no earlier than day 17 and receive G-CSF
SC beginning at the completion of PBSC re-infusion and continuing until blood counts
recover.

- Cohort II: Patients undergo PBSC mobilization and receive treatment as in cohort I.
Patients also receive paclitaxel IV over 3 hours on day 9.

- Cohort III: Patients undergo PBSC mobilization and receive unlabeled MOAB Lym-1, In111
MOAB Lym-1, Y90 MOAB Lym-1, and cyclosporine as in cohort I and paclitaxel as in cohort
II. Patients undergo autologous PBSC transplantation no earlier than day 17. Patients
receive G-CSF after transplantation as in cohort I.

- Cohort IV: Patients undergo PBSC mobilization and receive treatment as in cohort III.
Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or
unacceptable toxicity.

Cohorts of 1 to 3 patients receive escalating doses of Y90 MOAB Lym-1 until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 3 patients
require PBSC transplantation, or the dose preceding that at which 2 of 3 patients experience
dose-limiting toxicity.

Patients are followed monthly for 3 months, every 3 months for 1 year, every 6 months for 1
year, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study within 36 months.