Vismodegib After Stem Cell Transplant in Treating Patients With High-Risk First Remission or Relapsed Multiple Myeloma
Vismodegib After Stem Cell Transplant in Treating Patients With High-Risk First Remission or Relapsed Multiple Myeloma
This phase I trial studies how well vismodegib after stem cell transplant works in treating
 patients with high-risk first remission or relapsed multiple myeloma. Vismodegib may slow the
 growth of cancer cells. Giving vismodegib after autologous stem cell transplant may kill more
 multiple myeloma cells.
PRIMARY OBJECTIVES:

 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.

 SECONDARY OBJECTIVES:

 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.

 OUTLINE:

 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.
Inclusion Criteria:

 -  Patients must have histologically or cytologically confirmed multiple myeloma meeting
 criteria with symptomatic disease requiring treatment; patients considered to have
 high risk disease (defined as chromosome 13 deletion by cytogenetics; t(4;14),
 t(14;16) or 17p deletion by fluorescence in situ hybridization [FISH], B2-M > 5.5
 g/dL, immunoglobulin A [IgA] phenotype) in first remission (>= partial remission [PR])
 or patients with relapsed myeloma responding to salvage therapy (>= PR) based on the
 International Uniform Response Criteria are eligible

 -  Patients must have measurable disease utilizing serum or urine protein electrophoresis
 or serum kappa / lambda light chain assay

 -  Patients must be planning to proceed to single autologous transplantation according to
 institutional standards and must receive this transplantation prior to implementation
 of GDC-0449

 -  Concomitant bisphosphonate use is allowed as clinically indicated

 -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

 -  Life expectancy of greater than 6 months

 -  Women of child-bearing potential and men must use two forms of contraception (i.e.,
 barrier contraception and one other method of contraception) at least 4 weeks prior to
 GDC-0449 treatment, for the duration of study participation, and for at least 12
 months post-treatment; should a woman become pregnant or suspect she is pregnant while
 participating in this study, she should inform her treating physician immediately

 -  Women of childbearing potential are required to have a negative serum pregnancy
 test (with a sensitivity of at least 25 mIU/mL) within 10-14 days and within 24
 hours prior to the first dose of GDC-0449 (serum or urine); a pregnancy test
 (serum or urine) will be administered every 4 weeks if their menstrual cycles are
 regular or every 2 weeks if their cycles are irregular while on study within the
 24-hour period prior to the administration of GDC-0449; a positive urine test
 must be confirmed by a serum pregnancy test; prior to dispensing GDC-0449, the
 investigator must confirm and document the patient's use of two contraceptive
 methods, dates of negative pregnancy test, and confirm the patient understands of
 GDC-0449 cause serious or life-threatening birth defects

 -  Women of childbearing potential are defined as follows:

 -  Patients with regular menses

 -  Patients with amenorrhea, irregular cycles, or using a contraceptive method
 that precludes withdrawal bleeding

 -  Women who have had a tubal ligation

 -  Women are considered not to be of childbearing potential for the following
 reasons:

 -  The patient has undergone hysterectomy and/or bilateral oophorectomy

 -  The patient is post-menopausal defined by amenorrhea for at least 1 year in
 a women

 -  Human immunodeficiency virus (HIV)-positive patients without a prior acquired immune
 deficiency syndrome (AIDS)-defining illness and a CD4 count 400/millimeter^3 and
 either do not require anti-HIV therapy or are taking anti-HIV therapy that would not
 interfere with GDC-0449 (e.g. not taking zidovudine, protease inhibitors or
 non-nucleoside reverse transcriptase inhibitors) are eligible

 -  Ability to understand and the willingness to sign a written informed consent document