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Relapsed/Refractory Multiple MyelomaPhase 1NCT01794507

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

A Phase 1 study testing ABT-199, bortezomib and dexamethasone in people with Relapsed/Refractory Multiple Myeloma, run by AbbVie at 9 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Relapsed/Refractory Multiple Myeloma
What is being tested?
ABT-199, bortezomib and dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
9 sitesin 3 countries
Study dates
19 Nov 2012to 16 Jul 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

9 sites in 3 countries.

9 sites in 3 countries

United States5 sites

  • University of Michigan Hospitals /ID# 80353

    Ann Arbor, Michigan, 48109

  • Northwestern University Feinberg School of Medicine /ID# 117477

    Chicago, Illinois, 60611-2927

  • Mayo Clinic /ID# 121495

    Jacksonville, Florida, 32224

  • Mayo Clinic - Rochester /ID# 77235

    Rochester, Minnesota, 55905-0001

  • University of Arizona Cancer Center - North Campus /ID# 117876

    Tucson, Arizona, 85719-1478

Other trials in United States

Australia2 sites

  • Peter MacCallum Cancer Ctr /ID# 79553

    Melbourne, Victoria, 3000

  • Royal Melbourne Hospital /ID# 79533

    Parkville, Victoria, 3050

Other trials in Australia

France2 sites

  • CHRU Lille - Hôpital Claude Huriez /ID# 77234

    Lille, Hauts-de-France, 59045

  • CHU de Nantes, Hotel Dieu -HME /ID# 78773

    Nantes, 44093

Other trials in France

About this study

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

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.

Being tested
ABT-199, bortezomib, dexamethasone
Keywords
relapsed/refractory multiple myeloma, relapsed multiple myeloma, refractory multiple myeloma, multiple myeloma
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ABT-199Drug

    ABT-199 at cohort-defined dosing schedules and dose levels. ABT-199 at defined dose and schedule for Safety Expansion cohort

  • bortezomibDrug

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

  • dexamethasoneDrug

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

Study groups in NCT01794507
Study groupRoleWhat they receive
ABT-199 + BTZ/Dex Dose Escalation CohortsExperimentalEvaluate the safety and pharmacokinetics profile of ABT-199 administered with standard therapy bortezomib and dexamethasone in a dose escalation scheme in approximately 54 subjects.
Receives: Drug: ABT-199; Drug: bortezomib; Drug: dexamethasone
ABT-199 + BTZ/Dex Safety Expansion CohortExperimentalSafety expansion cohort to further evaluate recommended phase two dose (RPTD) of ABT-199 administered with standard therapy bortezomib and dexamethasone in approximately 12 subjects.
Receives: Drug: ABT-199; Drug: bortezomib; Drug: dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determination of peak concentration (Cmax) of ABT-199

    Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints

    Measured: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8

  2. Determine maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of ABT-199

    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.

    Measured: Minimum first cycle of dosing (21 days)

  3. Number of participants with adverse events

    Collect all adverse events at each visit.

    Measured: 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.

  4. Determination of trough concentration (Ctrough) of ABT-199

    Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints

    Measured: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8

  5. Determination of area under the concentration versus time curve (AUC) of ABT-199

    Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints

    Measured: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8

  6. Determine recommended phase two dose (RPTD) of ABT-199

    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.

    Measured: Minimum first cycle of dosing (21 days

Secondary outcomes (3)

  1. Duration of Response

    Number of days from the day of initial response is objectively documented to the day that disease progression is objectively documented

    Measured: Measured up to 48 months after the last subject has enrolled in the study

  2. Objective Response Rate

    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)

    Measured: Measured up to 48 months after the last subject has enrolled in the study

  3. Time to Disease Progression

    Number of days from the date of the first dose of ABT-199 to the date of the subject's disease progression.

    Measured: Measured up to 48 months after the last subject has enrolled in the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Feb 2013 (estimated)
  2. Study start19 Nov 2012
  3. Primary completion16 Jul 2019
  4. Study completion16 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01794507
Sponsor's protocol ID
M12-901
Other IDs
2011-004626-10
Status last verified
Jul 2021
First submitted
13 Dec 2012
Last updated
2 Aug 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Moreau P, Chanan-Khan A, Roberts AW, Agarwal AB, Facon T, Kumar S, Touzeau C, Punnoose EA, Cordero J, Munasinghe W, Jia J, Salem AH, Freise KJ, Leverson JD, Enschede SH, Ross JA, Maciag PC, Verdugo M, Harrison SJ. Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM. Blood. 2017 Nov 30;130(22):2392-2400. doi: 10.1182/blood-2017-06-788323. Epub 2017 Aug 28.

    PubMed 28847998

  • Matulis SM, Gupta VA, Nooka AK, Hollen HV, Kaufman JL, Lonial S, Boise LH. Dexamethasone treatment promotes Bcl-2 dependence in multiple myeloma resulting in sensitivity to venetoclax. Leukemia. 2016 May;30(5):1086-93. doi: 10.1038/leu.2015.350. Epub 2015 Dec 28.

    PubMed 26707935

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ABT-199, bortezomib and dexamethasone in people with Relapsed/Refractory Multiple Myeloma, run by AbbVie at 9 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Australia, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01794507, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2021.

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