DS Stage I Plasma Cell MyelomaPhase 1NCT01330173
Vismodegib After Stem Cell Transplant in Treating Patients With High-Risk First Remission or Relapsed Multiple Myeloma
A Phase 1 study testing Vismodegib, Pharmacological Study and Laboratory Biomarker Analysis in people with DS Stage I Plasma Cell Myeloma and DS Stage II Plasma Cell Myeloma, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma
- What is being tested?
- Vismodegib, Pharmacological Study and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2010to Nov 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Baltimore, Maryland, 21231
About this study
Official title: A Phase 1b Study of GDC-0449 Following Autologous Transplantation in 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
- Conditions
- DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- Being tested
- Vismodegib, Pharmacological Study, Laboratory Biomarker Analysis
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VismodegibDrug
Also called Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449
Given PO
Also called pharmacological studies
Correlative studies
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (vismodegib) | Experimental | 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. Receives: Drug: Vismodegib; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 6 months
Secondary outcomes (3)
Pharmacokinetics of vismodegib
Measured: Days 1 and 15
Pharmacodynamics of vismodegib
Measured: Up to 4 weeks after completion of study treatment
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.
Measured: From treatment initiation to the date of progression, assessed up to 4 weeks after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2011 (estimated)
- Study startDec 2010
- Primary completionOct 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DS Stage I Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Carol Huff, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01330173
- Sponsor's protocol ID
- NCI-2012-02914
- Other IDs
- NCI-2012-02914, NA_00040967, JHOC-J1067, NA_00040967 / J1067, CDR0000691708, J1067, 8414, U01CA070095
- Status last verified
- Sep 2014
- First submitted
- 5 Apr 2011
- Last updated
- 23 Dec 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of GDC-0449 Following Autologous Transplantation in Patients With High Risk First Remission or Relapsed Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01330173
- Acronym / sponsor ID
- NCI-2012-02914
- Conditions
- DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2010
- Primary completion
- Oct 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 6 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (vismodegib) | Experimental | Drug: Vismodegib, Other: Pharmacological Study, Other: Laboratory Biomarker AnalysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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%)
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VismodegibAlso: Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449Given PO | Drug | Treatment (vismodegib) |
| Pharmacological StudyAlso: pharmacological studiesCorrelative studies | Other | Treatment (vismodegib) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (vismodegib) |
Primary outcome
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.
3 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2014.
Related trials for DS Stage I Plasma Cell Myeloma
Active, not recruitingPhase 3
Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple Myeloma
DS Stage I Multiple Myeloma, DS Stage II Multiple Myeloma
Active, not recruitingPhase 3
Lenalidomide in Treating Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant
DS Stage I Multiple Myeloma, DS Stage II Multiple Myeloma
RecruitingPhase 3
Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial
Plasma Cell Myeloma, RISS Stage I Plasma Cell Myeloma
Active, not recruitingPhase 3
Lenalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Multiple Myeloma
DS Stage I Multiple Myeloma, DS Stage II Multiple Myeloma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carol Huff principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vismodegib, Pharmacological Study and Laboratory Biomarker Analysis in people with DS Stage I Plasma Cell Myeloma and DS Stage II Plasma Cell Myeloma, run by National Cancer Institute (NCI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in MM CSC counts (time frame: Baseline to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2014.