A Phase 1b Study of GDC-0449 Following Autologous Transplantation in Patients With High Risk First Remission or Relapsed Multiple Myeloma
I. To determine if GDC-0449 is able to reduce myeloma cancer stem cells (CSC) when given to
patients with MM following autologous stem cell transplantation.
I. To determine whether GDC-0449 is inhibiting the Hh pathway in patients with MM following
autologous transplantation by measuring downstream targets of Hh using qRT-PCR on plasma
cells and MM CSC obtained from blood and bone marrow of patients undergoing treatment.
II. To determine whether changes in MM CSC as measured by clonogenic assays on bone marrow
are seen in response to GDC-0449 and whether these changes predict recurrence.
III. To determine whether changes in MM CSC can be measured with similar or better accuracy
using peripheral blood flow cytometry as compared to bone marrow clonogenic assays.
IV. To determine the safety and toxicity profile for treatment with GDC-0449 following
autologous transplantation in patients with high risk or relapsed MM.
V. To characterize the pharmacokinetics (PK) of GDC-0449 (total and unbound) at steady-state
and correlate this with pharmacodynamic (PD) endpoints.
VI. To determine the one year progression free survival for patients given GDC-0449
following autologous transplantation.
OUTLINE: This is a multicenter study.
Patients receive Hedgehog antagonist GDC-0449 orally (PO) once daily on days 1-28. Treatment
repeats every 28 days for up to 11 courses in the absence of disease progression or
Patients undergo blood and bone marrow sample collection at baseline and periodically during
study for pharmacokinetic and other correlative studies.
After completion of treatment, patients are followed up for 4 weeks.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in MM CSC counts
Estimated using a simple linear regression model.
Baseline up to 6 months
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
United States: Food and Drug Administration
|University of Maryland Greenebaum Cancer Center||Baltimore, Maryland 21201|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital||Baltimore, Maryland 21231|