CompletedNCT01495351Updated Sep 25, 2017

Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma

A Phase 1 interventional study of ABT-888/Bortezomib in Multiple Myeloma, sponsored by AHS Cancer Control Alberta. Completed at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-09-25.

Sponsored by AHS Cancer Control Alberta · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 19
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study summary

The combination of PARP inhibitor (ABT-888) with a proteasome inhibitors (bortezomib) have demonstrated significant anti-myeloma effects in preclinical lab and animal studies. The goal of this phase I trial is to evaluate in patients with relapsed or refractory multiple myeloma the safety, toxicity profile and tolerability of ABT-888 (Veliparib) administered on a schedule including twice daily oral dosing for 14 days followed by 1 week rest in combination with standard dosing of Bortezomib.

Read the detailed description

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.

Conditions studied

Multiple Myeloma

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Multiple Myeloma 3,712

In context

Multiple Myeloma

3,712 studies on the registry are indexed under Multiple Myeloma; 752 are open to participants now.

This study's enrollment of 19 is below the median of 41 across 2,965 interventional studies indexed under Multiple Myeloma.

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Lead sponsor

AHS Cancer Control Alberta is the lead sponsor of 187 studies on the registry; 31 are open to participants now.

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

Who can participate

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

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Confirmed diagnosis of multiple myeloma.
Measurable disease, according to the International Myeloma Working Group criteria.
ECOG performance status 0, 1 or 2.
Patients must have received prior treatment for MM and have relapsed or progressed on prior therapy; no limit on number of prior treatment regimens, but prior treatment must be completed 2 weeks prior to registration. Prior exposure to Bortezomib is not an exclusion criteria as long as patients did not progress or relapse while receiving or within 3 months of completing trt with bortezomib
Prior radiation, completed at least 4 weeks prior to registration, is permitted.
Adequate marrow reserve, liver and renal function

Exclusion criteria

Exclusion Criteria:

patients with a history of other malignancies, except: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, prostate cancer with stable PSA for > 3 years, or other solid tumours curatively treated with no evidence of disease for > 5 years.
Patients with preexisting grade 2 (or higher) sensory neuropathy or grade 1 sensory neuropathy with neuropathic pain.
Pregnant or lactating women
Patients receiving concurrent treatment with other anti-cancer therapy any other investigational agents.
Active or uncontrolled infections
Patient with known documented congenital or acquired risk factor for thromboembolic event
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 19 participants (actual)

Study arms

Experimental
ABT-888/Bortezomib
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.
Drug: ABT-888/Bortezomib

Interventions

DrugABT-888/Bortezomib
Drug pages: Veliparib · Bortezomib
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.

What researchers measure

Primary outcomes

Determine the maximum tolerated dose (MTD) of ABT-888.
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.
Time frame: 21 Day Cycle
Identify the Dose Limiting Toxicities (DLT) of ABT-888
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.
Time frame: 21 Day Cycle

Secondary outcomes

Activity Objective - Preliminary assessment of the anti-tumor activity of ABT-888
Response to study drugs is assessed at the end of each cycle according to the International Myeloma Working Group (IMWG) response criteria.
Time frame: 21 day cycle
Exploratory Objective - Preliminary assessment of potential biomarkers
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.
Time frame: 24 months
Exploratory Objective - Determine in vivo the effect of ABT-888 on PARP inhibitors.
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).
Time frame: 24 Months
Determine invivo the effects of Bortezomib on the plasma cells DNA genes expression and function
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.
Time frame: 24 Months

Study locations

1 site

Tom Baker Cancer Centre
Calgary, Alberta T2N 4N2, Canada

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Oct 2011 to primary completion in Feb 2015, 40 months.

Of 197 non-industry phase 1 interventional studies under Multiple Myeloma, half reached primary completion within 57 months of starting (the median), counting those still running; a quarter within 39 and three quarters within 99. This study's 40 months is below that.

Counting every sponsor, half of 402 studies reached it within 50 months; a quarter within 32 and three quarters within 76.

How these figures are worked out, and which studies are left out of them.

Registered: Nov 16, 2011
First posted: Dec 20, 2011
StartActual: Oct 2011
Primary completionActual: Feb 2015
CompletionActual: Feb 10, 2015
Last update: Sep 25, 2017

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Sep 25, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01495351
Lead sponsor: AHS Cancer Control Alberta
Collaborators: Tom Baker Cancer Centre, Abbott
Responsible party: Sponsor
First posted: Dec 20, 2011
Start date: Oct 2011
Primary completion: Feb 2015
Completion: Feb 10, 2015
Last update: Sep 25, 2017

Study contacts

Nizar J Bahlis, M.D.

study chair · Tom Baker Cancer Centre, University of Calgary

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2017. You cannot join it, but the record below documents what was studied.

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Studies of the drugs tested here: Veliparib · Bortezomib

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