Vismodegib After Stem Cell Transplant in Treating Patients With High-Risk First Remission or Relapsed Multiple Myeloma
|DS Stage I Plasma Cell Myeloma DS Stage II Plasma Cell Myeloma DS Stage III Plasma Cell Myeloma Refractory Plasma Cell Myeloma||Drug: Vismodegib Other: Pharmacological Study Other: Laboratory Biomarker Analysis||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase 1b Study of GDC-0449 Following Autologous Transplantation in Patients With High Risk First Remission or Relapsed Multiple Myeloma|
- Change in MM CSC counts [ Time Frame: Baseline to 6 months ]Estimated using a simple linear regression model. The proportion of patients with negative slope estimates, indicating decline in MM CSC counts over study evaluations will be estimated.
- Pharmacokinetics of vismodegib [ Time Frame: Days 1 and 15 ]
- Pharmacodynamics of vismodegib [ Time Frame: Up to 4 weeks after completion of study treatment ]
- Time to progression [ Time Frame: From treatment initiation to the date of progression, assessed up to 4 weeks after completion of study treatment ]Estimated based on Kaplan-Meier and compared using the nonparametric, log-rank test, with proportional hazards regression used to model the effect of other correlations on the outcome of progression free survival (PFS). Median PFS will reported along with hazard ratios and corresponding 95% confidence intervals.
|Study Start Date:||December 2010|
|Study Completion Date:||November 2014|
|Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (vismodegib)
Patients receive vismodegib PO QD on days 1-28. Treatment repeats every 28 days for up to 11 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Pharmacological Study
Other Name: pharmacological studiesOther: Laboratory Biomarker Analysis
I. To determine if GDC-0449 (vismodegib) is able to reduce myeloma cancer stem cells (CSC) when given to patients with multiple myeloma (MM) following autologous stem cell transplantation.
I. To determine whether GDC-0449 is inhibiting the hedgehog (Hh) pathway in patients with MM following autologous transplantation by measuring downstream targets of Hh using quantitative reverse transcriptase polymerase chain reaction (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.
Patients receive vismodegib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 11 courses in the absence of disease progression or unacceptable toxicity.
After completion of treatment, patients are followed up for 4 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01330173
|United States, Maryland|
|University of Maryland/Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21231|
|Principal Investigator:||Carol Huff||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital|