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A Study Evaluating ABT-199 in Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Standard Therapy

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ClinicalTrials.gov Identifier: NCT01794507
Recruitment Status : Suspended (Safety)
First Posted : February 20, 2013
Last Update Posted : March 21, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

Brief Summary:
The primary objectives of this study are to assess the safety profile, characterize pharmacokinetics (PK) and determine the dosing schedule, maximum tolerated dose (MTD), and the recommended phase two dose (RPTD) of ABT-199 when administered in subjects with relapsed /refactory multiple myeloma who are receiving bortezomib and dexamethasone as their standard therapy.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Multiple Myeloma Drug: ABT-199 Drug: bortezomib Drug: dexamethasone Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Relapsed or Refractory Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Their Standard Therapy
Actual Study Start Date : November 19, 2012
Estimated Primary Completion Date : March 29, 2019
Estimated Study Completion Date : March 29, 2019


Arm Intervention/treatment
Experimental: ABT-199 + BTZ/Dex Dose Escalation Cohorts
Evaluate the safety and pharmacokinetics profile of ABT-199 administered with standard therapy bortezomib and dexamethasone in a dose escalation scheme in approximately 54 subjects.
Drug: ABT-199
ABT-199 at cohort-defined dosing schedules and dose levels. ABT-199 at defined dose and schedule for Safety Expansion cohort

Drug: bortezomib
Bortezomib at cohort-defined dosing schedules and dose levels. Bortezomib at defined dose and schedule for Safety Expansion cohort

Drug: dexamethasone
Dexamethasone at cohort-defined dosing schedules and dose levels. Dexamethasone at defined dose and schedule for Safety Expansion cohort.

Experimental: ABT-199 + BTZ/Dex Safety Expansion Cohort
Safety expansion cohort to further evaluate recommended phase two dose (RPTD) of ABT-199 administered with standard therapy bortezomib and dexamethasone in approximately 12 subjects.
Drug: ABT-199
ABT-199 at cohort-defined dosing schedules and dose levels. ABT-199 at defined dose and schedule for Safety Expansion cohort

Drug: bortezomib
Bortezomib at cohort-defined dosing schedules and dose levels. Bortezomib at defined dose and schedule for Safety Expansion cohort

Drug: dexamethasone
Dexamethasone at cohort-defined dosing schedules and dose levels. Dexamethasone at defined dose and schedule for Safety Expansion cohort.




Primary Outcome Measures :
  1. Determination of peak concentration (Cmax) of ABT-199 [ Time Frame: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8 ]
    Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints

  2. Determine maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of ABT-199 [ Time Frame: Minimum first cycle of dosing (21 days) ]
    ABT-199 will be dose-escalated until the largest dose is reached that is determined to be safe based on adverse event reporting and dose-limiting toxicities information from all subjects.

  3. Number of participants with adverse events [ Time Frame: From subject's first dose of ABT-199 until 30 days after subject's last dose of ABT-199; up to 2 years following last subject first dose. ]
    Collect all adverse events at each visit.

  4. Determination of trough concentration (Ctrough) of ABT-199 [ Time Frame: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8 ]
    Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints

  5. Determination of area under the concentration versus time curve (AUC) of ABT-199 [ Time Frame: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8 ]
    Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints

  6. Determine recommended phase two dose (RPTD) of ABT-199 [ Time Frame: Minimum first cycle of dosing (21 days ]
    ABT-199 will be dose-escalated until the largest dose is reached that is determined to be safe based on adverse event reporting and dose-limiting toxicities information from all subjects.


Secondary Outcome Measures :
  1. Duration of Response [ Time Frame: Measured up to 48 months after the last subject has enrolled in the study ]
    Number of days from the day of initial response is objectively documented to the day that disease progression is objectively documented

  2. Objective Response Rate [ Time Frame: Measured up to 48 months after the last subject has enrolled in the study ]
    The proportion of subjects with response using International Myeloma Working Group (IMWG) response criteria will be computed for all subjects with active disease at baseline (in the opinion of the investigator)

  3. Time to Disease Progression [ Time Frame: Measured up to 48 months after the last subject has enrolled in the study ]
    Number of days from the date of the first dose of ABT-199 to the date of the subject's disease progression.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 1
  • Diagnosis of multiple myeloma previously treated with at least 1 prior line of therapy (dose escalation only) or (safety expansion only) received treatment with a proteasome inhibitor or an IMiD(r) or immunomodulatory agent (e.g., thalidomide, lenalidomide). Induction therapy and following stem cell transplant are considered a single line of therapy.
  • Measurable disease at Screening: Serum monoclonal protein greater than or equal to 1 g/dL by protein electrophoresis, or greater than or equal to 200 mg monoclonal protein in the urine on 24-hr electrophoresis, or serum immunoglobulin free light chain greater than or equal to 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio.
  • Subjects with a history of autologous or allogenic stem cell transplant must have adequate bone marrow independent of any growth factor support, and have recovered from any transplant related toxicity(s); and either greater than 100 days post-autologous transplant (prior to first dose of study drug) or greater than or equal to 6 months post-allogenic transplant (prior to first dose of study drug) and not have active graft-versus-host disease (i.e., requiring treatment).
  • Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening.

Exclusion Criteria:

  • Exhibits evidence of other clinically significant uncontrolled condition(s), including, but not limited to: uncontrolled systemic infection (viral, bacterial, or fungal), diagnosis of fever and neutropenia within 1 week prior to first dose of study drug
  • Cardiovascular disability status of New York Heart Association Class greater than or equal to 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea or anginal pain.
  • Significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, pulmonary or hepatic disease, that in the opinion of the investigator, would adversely affect his/her participation in the study.
  • History of other active malignancies other than multiple myeloma within the past 3 years prior to study entry, with the following exceptions: adequately treated in situ carcinoma of the cervix uteri, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  • Tested positive for HIV or hepatitis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01794507


Locations
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United States, Arizona
University Arizona Cancer Ctr /ID# 117876
Tucson, Arizona, United States, 85719-1478
United States, Florida
Mayo Clinic /ID# 121495
Jacksonville, Florida, United States, 32224
United States, Illinois
Northwestern University Feinberg School of Medicine /ID# 117477
Chicago, Illinois, United States, 60611-2927
United States, Michigan
University of Michigan Hospitals /ID# 80353
Ann Arbor, Michigan, United States, 48109-5008
United States, Minnesota
Mayo Clinic - Rochester /ID# 77235
Rochester, Minnesota, United States, 55905-0001
Australia, Victoria
Peter MacCallum Cancer Ctr /ID# 79553
Melbourne, Victoria, Australia, 3000
Royal Melbourne Hospital /ID# 79533
Parkville, Victoria, Australia, 3050
France
CHRU Lille - Hôpital Claude Huriez /ID# 77234
Lille CEDEX, Hauts-de-France, France, 59045
CHU de Nantes, Hotel Dieu -HME /ID# 78773
Nantes, France, 44093
Sponsors and Collaborators
AbbVie
Genentech, Inc.
Investigators
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Study Director: AbbVie Inc. AbbVie

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT01794507     History of Changes
Other Study ID Numbers: M12-901
2011-004626-10 ( EudraCT Number )
First Posted: February 20, 2013    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by AbbVie:
relapsed/refractory multiple myeloma
relapsed multiple myeloma
refractory multiple myeloma
multiple myeloma

Additional relevant MeSH terms:
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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
Dexamethasone acetate
Bortezomib
Venetoclax
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents