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

NCT01495351 | Completed Phase 1 DMC

• 2 other identifiers: MM11-01E24055
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  21 Day Cycle

Secondary Outcomes (4)

• Activity Objective - Preliminary assessment of the anti-tumor activity of ABT-888

  21 day cycle

• Exploratory Objective - Preliminary assessment of potential biomarkers

  24 months

• Exploratory Objective - Determine in vivo the effect of ABT-888 on PARP inhibitors.

  24 Months

• Determine invivo the effects of Bortezomib on the plasma cells DNA genes expression and function

  24 Months

Study Arms (1)

ABT-888/Bortezomib

EXPERIMENTAL

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

ABT-888/Bortezomib DRUG

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.

ABT-888/Bortezomib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of multiple myeloma.
• Measurable disease, according to the International Myeloma Working Group criteria.
• ECOG performance status 0, 1 or 2.

You may not qualify if:

• Prior radiation, completed at least 4 weeks prior to registration, is permitted.
• Adequate marrow reserve, liver and renal function
• 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

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead
• Tom Baker Cancer Centre: collaborator
• Abbott: collaborator

Study Sites (1)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Nizar J Bahlis, M.D.

  Tom Baker Cancer Centre, University of Calgary

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2011
• First Posted: December 20, 2011
• Study Start: October 1, 2011
• Primary Completion: February 1, 2015
• Study Completion: February 10, 2015
• Last Updated: September 25, 2017

Record last verified: 2017-09

Locations

CA (1)