Vismodegib After Stem Cell Transplant in Treating Patients With High-Risk First Remission or Relapsed Multiple Myeloma
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Purpose
This phase I trial is studying how well GDC-0449 works in treating patients with high-risk first remission or relapsed multiple myeloma who received an autologous stem cell transplant. GDC-0449 may slow the growth of cancer cells. Giving GDC-0449 after autologous stem cell transplant may kill more multiple myeloma cells
| Condition | Intervention | Phase |
|---|---|---|
|
Smoldering Multiple Myeloma Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma |
Other: pharmacological study Drug: vismodegib Other: laboratory biomarker analysis |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: 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 up to 6 months ] [ Designated as safety issue: No ]Estimated using a simple linear regression model.
- Pharmacokinetic assessments of vismodegib [ Time Frame: Days 1 and 15 ] [ Designated as safety issue: No ]
- Pharmacodynamic assessments of vismodegib [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 38 |
| Study Start Date: | December 2010 |
| Estimated Primary Completion Date: | January 2100 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: ARM I
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 unacceptable toxicity.
|
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Drug: vismodegib
Given orally
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Detailed Description:
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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 unacceptable toxicity.
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 FISH, B2-M > 5.5 g/dL, IgA phenotype) in first 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
- Life expectancy of greater than 6 months
- ECOG performance status =< 2 (Karnofsky >= 60%)
- The effects of GDC-0449 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because Hh signal pathway inhibitors as well as other therapeutic agents used in this trial are known to cause interruption of the embryonic signaling pathway and may lead to serious or life-threatening birth defects, including brain deformities, facial malformation, heart problems, or abnormal organs; therefore, 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
- HIV-positive patients without a prior 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
Exclusion Criteria:
- Ability to understand and the willingness to sign a written informed consent document
Contacts and Locations| United States, Maryland | |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital | Recruiting |
| Baltimore, Maryland, United States, 21231 | |
| Contact: Carol A. Huff 443-287-7104 huffca@jhmi.edu | |
| Principal Investigator: Carol A. Huff | |
| University of Maryland Greenebaum Cancer Center | Recruiting |
| Baltimore, Maryland, United States, 21201-1595 | |
| Contact: Ashraf Z. Badros 410-328-1230 abadros@umm.edu | |
| Principal Investigator: Ashraf Z. Badros | |
| Principal Investigator: | Carol Huff | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01330173 History of Changes |
| Other Study ID Numbers: | NCI-2012-02914, J1067, U01CA070095 |
| Study First Received: | April 5, 2011 |
| Last Updated: | February 6, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases |
Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases |
ClinicalTrials.gov processed this record on May 19, 2013