CClinicalTrials.gg
CompletedNCT01330173Updated Dec 23, 2014

Vismodegib After Stem Cell Transplant in Treating Patients With High-Risk First Remission or Relapsed Multiple Myeloma

A Phase 1 interventional study of Vismodegib and Pharmacological Study in DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma and DS Stage III Plasma Cell Myeloma, sponsored by National Cancer Institute (NCI). Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-12-23.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
50
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • DS Stage I Plasma Cell Myeloma
  • DS Stage II Plasma Cell Myeloma
  • DS Stage III Plasma Cell Myeloma
  • Refractory Plasma Cell Myeloma
03

In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 50 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
50 participants (actual)

Study arms

  • 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.

    Drug: Vismodegib · Other: Pharmacological Study · Other: Laboratory Biomarker Analysis

Interventions

  • DrugVismodegib

    Given PO

    Also known as: Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449

  • OtherPharmacological Study

    Correlative studies

    Also known as: pharmacological studies

  • OtherLaboratory Biomarker Analysis

    Correlative studies

06

What researchers measure

Primary outcomes

  1. Change in MM CSC counts

    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.

    Time frame: Baseline to 6 months

Secondary outcomes

  1. Pharmacokinetics of vismodegib

    Time frame: Days 1 and 15

  2. Pharmacodynamics of vismodegib

    Time frame: Up to 4 weeks after completion of study treatment

  3. Time to progression

    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.

    Time frame: From treatment initiation to the date of progression, assessed up to 4 weeks after completion of study treatment

07

Study locations

2 sites
  • University of Maryland/Greenebaum Cancer Center
    Baltimore, Maryland 21201, United States
  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
    Baltimore, Maryland 21231, United States
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 23, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT01330173
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Apr 6, 2011
Start date
Dec 2010
Primary completion
Oct 2014
Completion
Nov 2014
Last update
Dec 23, 2014

Study contacts

Carol Huff
principal investigator · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2014. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion