Effect of AT7519M Alone and AT7519M Plus Bortezomib in Patients With Previously Treated Multiple Myeloma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Open-label Multicenter Study of AT7519M Alone and in Combination With Bortezomib in Patients With Previously Treated Multiple Myeloma|
- To evaluate the clinical efficacy of AT7519M alone or in combination with bortezomib [ Time Frame: Subjects with be followed until disease progression (an average of 4 cycles per subject. i.e an average of 84 days) ] [ Designated as safety issue: No ]Efficacy will be assessed using the International Multiple Myeloma Working Group (IMWG) Response Criteria
- Assess the type, incidence and severity of clinically significant treatment emergent adverse events as assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) V 4.03 [ Time Frame: Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days) ] [ Designated as safety issue: Yes ]
- To define the pharmacokinetic profile of AT7519M and bortezomib when administered alone or in combination with bortezomib [ Time Frame: 2 cycles (i.e an average of 42 days) ] [ Designated as safety issue: No ]The pharmacokinetic evaluation will include the calculation of plasma clearance and elimination phase half-life for AT7519M and bortezomib
- To identify the maximum tolerated dose (MTD) of AT7519M in combination with bortezomib [ Time Frame: Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days) ] [ Designated as safety issue: No ]The MTD will be based on the incidence of dose limiting toxicities
|Study Start Date:||November 2010|
|Study Completion Date:||March 2015|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Patients will be enrolled into 3 groups which will run sequentially. Groups A and B will receive AT7519M only, whereas Group C will receive AT7519M in combination with Bortezomib.
Part A: Nine patients will receive AT7519M as an intravenous infusion on days 1, 4, 8 and 11 of a three week cycle. The starting dose of AT7519M will be 21mg/m^2/dose and will be increased to 27mg/m^2/dose during subsequent cycles in the absence of AT7519M-related toxicities.
Part B: Amendment clarified there will be no further exploration of AT7519M as a monotherapy.
Part C: Amendment modified dose escalation to a conventional 3 + 3 design with a maximum total of 14 patients will be treated at the maximum tolerated dose.
Part C will treat between 3-26 patients with a combination of bortezomib and AT7519M in a dose escalation design. The starting doses for the dose escalation are bortezomib 1 mg/m2 and AT7519M 14 mg/m2.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01183949
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, MA02115|
|Dana Faber Cancer Institute|
|Boston, Massachusetts, United States|
|United States, New York|
|Memorial Sloan-Kettering Cancer Centre|
|New York, New York, United States, 10065|
|United States, Wisconsin|
|MCW and Froedtert Clinical Cancer Center, Division of Neoplastic Diseases & Related Disorders|
|Milwaukee, Wisconsin, United States, 53226|