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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by AHS Cancer Control Alberta.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Tom Baker Cancer Centre
Abbott
Information provided by (Responsible Party):
AHS Cancer Control Alberta
ClinicalTrials.gov Identifier:
NCT01495351
First received: November 16, 2011
Last updated: January 18, 2012
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: ABT-888/Bortezomib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma

Resource links provided by NLM:


Further study details as provided by AHS Cancer Control Alberta:

Primary Outcome Measures:
  • Determine the maximum tolerated dose (MTD) of ABT-888. [ Time Frame: 21 Day Cycle ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Activity Objective - Preliminary assessment of the anti-tumor activity of ABT-888 [ Time Frame: 21 day cycle ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 42
Study Start Date: January 2012
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01495351

Contacts
Contact: Nizar J Bahlis, MD 403-521-3072 nbahlis@ucalgary.ca
Contact: Syeda Abbas 403-521-3072 syeda.abbas@albertacancerboard.ab.ca

Locations
Canada, Alberta
Tom Baker Cancer Centre Recruiting
Calgary, Alberta, Canada, T2N 4N2
Principal Investigator: Nizar J Bahlis, M.D.         
Sub-Investigator: Peter Duggan, M.D.         
Sub-Investigator: Ernesta P Neri, M.D.         
Sponsors and Collaborators
AHS Cancer Control Alberta
Tom Baker Cancer Centre
Abbott
Investigators
Study Chair: Nizar J Bahlis, M.D. Tom Baker Cancer Centre, University of Calgary
  More Information

No publications provided

Responsible Party: AHS Cancer Control Alberta
ClinicalTrials.gov Identifier: NCT01495351     History of Changes
Other Study ID Numbers: MM11-01, E24055
Study First Received: November 16, 2011
Last Updated: January 18, 2012
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on August 28, 2014