Clinical trial NCT01495351: Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma
Official title: Phase I Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: AHS Cancer Control Alberta
Sponsor class: OTHER
Collaborators: name: Tom Baker Cancer Centre
name: Abbott
First posted: 2011-12-20
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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:

* 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

Primary outcomes:
measure: Determine the maximum tolerated dose (MTD) of ABT-888.
timeFrame: 21 Day Cycle
measure: Identify the Dose Limiting Toxicities (DLT) of ABT-888
timeFrame: 21 Day Cycle
Secondary outcomes:
measure: Activity Objective - Preliminary assessment of the anti-tumor activity of ABT-888
timeFrame: 21 day cycle
measure: Exploratory Objective - Preliminary assessment of potential biomarkers
timeFrame: 24 months
measure: Exploratory Objective - Determine in vivo the effect of ABT-888 on PARP inhibitors.
timeFrame: 24 Months
measure: Determine invivo the effects of Bortezomib on the plasma cells DNA genes expression and function
timeFrame: 24 Months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
Study officials:
affiliation: Tom Baker Cancer Centre, University of Calgary
name: Nizar J Bahlis, M.D.
role: STUDY_CHAIR
References: