- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01495351
Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma
Phase I Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma
Study Overview
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Alberta
-
Calgary, Alberta, Canada, T2N 4N2
- Tom Baker Cancer Centre
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
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 is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
21 Day Cycle
|
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.
|
21 Day Cycle
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
21 day cycle
|
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.
|
24 months
|
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).
|
24 Months
|
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.
|
24 Months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Nizar J Bahlis, M.D., Tom Baker Cancer Centre, University of Calgary
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Poly(ADP-ribose) Polymerase Inhibitors
- Bortezomib
- Veliparib
Other Study ID Numbers
- MM11-01
- E24055 (Other Identifier: CHREB- University of Calgary)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Myeloma
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
-
National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
Clinical Trials on ABT-888/Bortezomib
-
AbbVieCompletedAdvanced Solid TumorsJapan
-
National Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Breast Carcinoma | Ovarian Carcinoma | Pancreatic Carcinoma | Prostate Carcinoma | Recurrent Breast Carcinoma | Estrogen Receptor Negative | HER2/Neu Negative | Progesterone Receptor Negative | Triple-Negative... and other conditionsUnited States
-
National Cancer Institute (NCI)NRG OncologyCompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation Carrier | Ovarian Epithelial TumorUnited States
-
AbbVie (prior sponsor, Abbott)Prostate Cancer Clinical Trials ConsortiumCompleted
-
National Cancer Institute (NCI)Active, not recruitingAdvanced Malignant Solid NeoplasmUnited States
-
Radiation Therapy Oncology GroupNational Cancer Institute (NCI); NRG OncologyCompletedBrain and Central Nervous System TumorsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Peritoneal Carcinomatosis | Adult Solid NeoplasmUnited States, Canada
-
Northwestern UniversityBristol-Myers Squibb; National Cancer Institute (NCI); AbbVieUnknownUnresectable Solid Neoplasm | Recurrent Solid Neoplasm | Refractory Mantle Cell Lymphoma | Aggressive Non-Hodgkin Lymphoma | Advanced Solid Neoplasm | T-Cell Non-Hodgkin LymphomaUnited States
-
Georgetown UniversityAbbottUnknownMetastatic Pancreatic CancerUnited States
-
AbbVieNo longer availableHigh Grade Serous Ovarian Cancer | Solid Tumors With Documented BRCA, BARD, or PALB or Other Acceptable DNA Mutations or Anomalies That Are Scientifically Sound | Triple Negative Breast Cancer (TNBC) | Patients Requiring Veliparib Suspension Formulation