Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma
|ClinicalTrials.gov Identifier: NCT01495351|
Recruitment Status : Completed
First Posted : December 20, 2011
Last Update Posted : September 25, 2017
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: ABT-888/Bortezomib||Phase 1|
This is a dose-finding / dose escalation phase I trial of ABT-888 (Veliparib) in combination with Bortezomib and Dexamethasone in patients with relapsed or refractory multiple myeloma. ABT-888 is given orally (PO) twice daily (every 12 hours) for 14 days in a 21 days cycle.
First dose to be given within 1 hour of Bortezomib on day 1. Planned starting dose is 20 mg PO every 12 hours. Starting dose escalation is planned until an MTD is reached.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma|
|Actual Study Start Date :||October 2011|
|Primary Completion Date :||February 2015|
|Study Completion Date :||February 10, 2015|
U.S. FDA Resources
Patients will be on a treatment schedule including twice daily oral dosing for 14 days followed by 1 week rest in combination with standard dosing of Bortezomib and Dexamethasone in a 21 days cycle for a total of 14 cycles.
ABT-888 is given orally (PO) twice daily (every 12 hours) for 14 days in a 21 days cycle. First dose to be given within 1 hour of Bortezomib on day 1. Planned starting dose is 20 mg PO every 12 hours. Starting dose escalation is planned until an MTD is reached.
- Determine the maximum tolerated dose (MTD) of ABT-888. [ Time Frame: 21 Day Cycle ]Study follows a modified dose escalation scheme with a 3+3 design (3 to 6 patients per dose level or cohort). Only the ABT-888 dose will be escalated with a maximum dose of ABT-888 of 100 mg PO BID. If >1 out 6 patients at any dose level suffer dose limiting toxicity, then dose escalation is stopped, and this dose is declared as MTD. 3 additional patients will be entered at the next lowest dose level. The recommended phase 2 dose is defined as the dose level with ≤ 1 out of 6 patients experiencing DLTs at the highest dose level below the MTD.
- Identify the Dose Limiting Toxicities (DLT) of ABT-888 [ Time Frame: 21 Day Cycle ]All adverse events, including DLTs, are graded according to the NCI CTCAE, v4.0. A DLT is defined as any grade 3 or higher non-hematologic toxicity, or any grade 4 hematologic toxicity, considered by the investigator to be related to the study drugs and occurring during Days 1-22 of Cycle 1.
- Activity Objective - Preliminary assessment of the anti-tumor activity of ABT-888 [ Time Frame: 21 day cycle ]Response to study drugs is assessed at the end of each cycle according to the International Myeloma Working Group (IMWG) response criteria.
- Exploratory Objective - Preliminary assessment of potential biomarkers [ Time Frame: 24 months ]Gene expression profiling is performed at baseline and compared between responders versus non-responders in order to identify a "treatment response signature". 2.5 mg of RNA will be extracted from plasma cells sorted from pre-treatment (D1, cycle 1) (n=20) and post-treatment (D11, cycle 1) (n=20) bone marrow aspirates collected from patients treated in the extension cohort. cRNAs will be hybridized onto the U133 Plus 2.0 gene chips and raw data files acquired using Affymetrix Microarray Suite version 5.1 software and analyzed with the Partek Genomics Suite v6.4.
- Exploratory Objective - Determine in vivo the effect of ABT-888 on PARP inhibitors. [ Time Frame: 24 Months ]Poly-ADP-ribose (PAR) levels are measured in sorted CD138+ plasma cells from pre-ABT-888 treatment on day 1 cycle1, as well as post ABT-888 treatment (within 4-6 hours) on days 4 and 11. PAR levels will be measured by standardized ELISA assays (HT PARP in vivo Pharmacodynamic Assay II™, Trevigen).
- Determine invivo the effects of Bortezomib on the plasma cells DNA genes expression and function [ Time Frame: 24 Months ]Gene expression profiling is performed at baseline prior to treatment with bortezomib and on days 4 and 11 post bortezomib treatment. 2.5 mg of RNA will be extracted from plasma cells sorted from bone marrow aspirates collected from patients treated on trial. cRNAs will be hybridized onto the U133 Plus 2.0 gene chips and raw data files acquired using Affymetrix Microarray Suite version 5.1 software and analyzed with the Partek Genomics Suite v6.4.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01495351
|Tom Baker Cancer Centre|
|Calgary, Alberta, Canada, T2N 4N2|
|Study Chair:||Nizar J Bahlis, M.D.||Tom Baker Cancer Centre, University of Calgary|