A Pilot, Phase-I Trial of Rabbit Anti-Thymocyte Globulin (rATG, Thymoglobulin™) in Combination With Rapamycin in Relapsed Multiple Myeloma (MM)
- Determine the safety and tolerability, in terms of clinical and laboratory toxicity, of
anti-thymocyte globulin (ATG) combined with sirolimus in patients with relapsed
- Determine the dose-limiting toxicity of this regimen in these patients.
- Determine the maximum tolerated dose of ATG when administered with sirolimus in these
- Determine the clinical activity of this regimen, in terms of measurability of
improvement in clinical benefits, in these patients.
- Assess patients for sensitivity of CD 138^-positive myeloma cells to ATG prior to
- Determine the pharmacokinetics, in terms of ATG levels in blood and bone marrow, in
- Assess the binding capability of ATG to bone marrow resident myeloma cells.
- Determine if an ATG-resistant clone emerges after treatment.
OUTLINE: This is an open-label, pilot, dose-escalation study of anti-thymocyte globulin
Patients receive ATG IV over 6-12 hours for 4, 6, or 8 days and oral sirolimus once daily on
days 1-30 in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of ATG 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. At least 6 patients are treated at the MTD.
Bone marrow aspirates and blood samples are collected at baseline and periodically during
study treatment for drug sensitivity and pharmacokinetic studies.
After completion of study treatment, patients are followed every 3 weeks for up to 2 months
and then monthly thereafter.
PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity and maximum tolerated dose
Duration of the study
J. J. Ifthikharuddin, MD
James P. Wilmot Cancer Center
United States: Food and Drug Administration
|James P. Wilmot Cancer Center at University of Rochester Medical Center||Rochester, New York 14642|