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Multiple MyelomaPhase 1NCT02951117

A Study of Venetoclax and ABBV-838 Combination Therapy With Dexamethasone in Participants With Multiple Myeloma Whose Cancer Has Come Back or Had No Response to Recent Cancer Treatment

A Phase 1 study testing Venetoclax, ABBV-838 and Dexamethasone in people with Multiple Myeloma, run by AbbVie at 3 sites in Australia.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an open-label, multicenter clinical trial designed to evaluate the safety and potential efficacy of venetoclax and ABBV-838 combination therapy with dexamethasone in participants with relapsed or refractory multiple myeloma (MM) who have received 2 or more prior lines of therapy for multiple myeloma (MM). Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Multiple Myeloma
What is being tested?
Venetoclax, ABBV-838 and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
3 sitesAustralia
Study dates
31 Aug 2017to 28 Apr 2021
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 status less than or equal to 1 for participants in the dose escalation portion of the study and ECOG less than or equal to 2 in the dose expansion portion.
  • Received at least 2 prior therapies including an Immunomodulatory Thalidomide Derivative Compounds (IMiD) and a proteasome inhibitor.
  • Documented relapsed or progressive multiple myeloma on or after any regimen or is refractory to the most recent line of therapy.
  • Received at least 2 prior therapies including an IMiD and a proteasome inhibitor.
  • Documented relapsed or progressive multiple myeloma on or after any regimen or is refractory to the most recent line of therapy.
  • Eligible for and agree to bone marrow (BM) aspirate prior to treatment start and at designated times per protocol.
  • Measurable disease at Screening, defined as at least one of the following M component in serum (greater than or equal to 0.5 g/dL) and/or urine (greater than or equal to 0.2 g excreted in a 24 hour collection sample) or serum free light chain greater than or equal to 100 mg/dL with an abnormal κ/λ ratio of less than 0.26 or greater than 1.65.

Who cannot join

  • Received any anti-myeloma therapy (other than monoclonal antibodies), including chemotherapy, radiotherapy, biological, immunotherapy or an investigational therapy, including targeted small molecule agents within 5 half-lives (or 14 days if half-live unknown) prior to first dose of first dose of venetoclax, ABBV-838, and dexamethasone.
  • Received anti-myeloma monoclonal antibodies within 6 weeks prior to first dose of venetoclax, ABBV-838, and dexamethasone.
  • Has a significant history of renal, neurologic (peripheral neuropathy), psychiatric, endocrinologic (diabetes mellitus), metabolic, immunologic, cardiovascular, pulmonary or hepatic disease within the last 6 months.
  • Received corticosteroid therapy at a dose equivalent to greater than or equal to 4 mg/day of dexamethasone within 3 weeks prior to first dose.

Trial locations and contacts

3 sites in 1 country.

Australia3 sites

  • St Vincent´s Hospital /ID# 153022

    Darlinghurst, 2010

  • St. Vincents Hospital Melbourne /ID# 157925

    Fitzroy, 3065

  • The Alfred Hospital /ID# 150202

    Prahran, 3181

Other trials in Australia

About this study

Official title: A Phase 1b, Open Label, Multicenter, Dose Escalation Study of Venetoclax and ABBV-838 Combination Therapy With Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

This is an open-label, multicenter clinical trial designed to evaluate the safety and potential efficacy of venetoclax and ABBV-838 combination therapy with dexamethasone in participants with relapsed or refractory multiple myeloma (MM) who have received 2 or more prior lines of therapy for multiple myeloma (MM). The study will consist of 2 arms: Arm A and Arm B (if applicable). Each arm will have a dose escalation and dose expansion portion.

Read the detailed description

The study will consist of 2 arms: Arm A and Arm B (if applicable). Arm A dose escalation will investigate up to 3 doses of ABBV-838 at 3-week dosing intervals (Q3W) in combination with venetoclax and dexamethasone. Arm A dose expansion portion will investigate the ABBV-838 Q3W dosing interval with venetoclax and dexamethasone at the recommended phase two dose (RPTD) combination defined from the Dose Escalation portion.

Based on data from the ongoing ABBV-838 monotherapy study (Study M14-467) Arm B dose escalation may be conducted, if deemed necessary. If conducted, Arm B dose excalation will investigate up to 3 doses of ABBV-838 at either weekly (Q1W) or bi-weekly (Q2W) dosing intervals in combination with venetoclax and dexamethasone. Arm B dose expansion portion will investigate either the ABBV-838 Q1W or Q2W dosing interval in combination with venetoclax and dexamethasone at the RPTD combination defined from the Dose Escalation portion.

Being tested
Venetoclax, ABBV-838, Dexamethasone
Keywords
lymphoid malignancies, Next generation sequencing, Refractory Multiple Myeloma, Relapsed 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.

  • VenetoclaxDrug

    Also called ABT-199

    Tablet

  • ABBV-838Drug

    Intravenous infusion

  • DexamethasoneDrug

    Tablet or intravenous infusion

Study groups in NCT02951117
Study groupRoleWhat they receive
Arm A Venetoclax QD + ABBV-838 Q3W + DexamethasoneExperimentalABBV-838 administered at cohort-defined doses every 3 weeks (Q3W; starting dose 4.0 mg/kg) in combination with venetoclax (400 mg or 800 mg once daily [QD]) and dexamethasone (40 mg once weekly [Q1W]); once the maximum-tolerated-dose (MTD) and recommended phase two dose (RPTD) are determined, ABBV-838 in combination with venetoclax and dexamethasone at RPTD will be administered in a dose expansion phase of the study.
Receives: Drug: Venetoclax; Drug: ABBV-838; Drug: Dexamethasone
Arm B Venetoclax QD + ABBV-838 Q1W or Q2W + Dexamethasone Q1WExperimentalDose escalation portion will investigate either the ABBV-838 weekly (Q1W) or bi-weekly (Q2W) dosing interval in combination with venetoclax (400 or 800 mg QD) and dexamethasone (40 mg Q1W). The dose expansion portion will investigate either the ABBV-838 weekly (Q1W) or bi-weekly (Q2W) dosing interval in combination with venetoclax and dexamethasone at the RPTD combination defined from the Dose Escalation portion.
Receives: Drug: Venetoclax; Drug: ABBV-838; Drug: Dexamethasone

What is being measured

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

  1. Maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of venetoclax and ABBV-838 combination therapy when administered with dexamethasone

    The MTD and the RPTD of venetoclax and ABBV-838 combination therapy with dexamethasone will be determined during the dose escalation phase of the study. Once the RPTD combination has been determined, the dose expansion portion will begin.

    Measured: Minimum first cycle of dosing (21 or 28 days, depending on arm)

  2. Number of participants with adverse events

    Measured: Up to approximately 2 years following the first dose of the last subject enrolled

Secondary outcomes (12)

  1. Maximum observed plasma concentration (Cmax) of venetoclax

    Measured: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

  2. Time to Cmax (Tmax) of venetoclax

    Measured: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

  3. Area under the plasma concentration-time curve over the 24-hour dose interval (AUC0-24) of venetoclax

    Measured: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

  4. Objective Response Rate (ORR)

    The Objective Response Rate (ORR) is defined as the proportion of subjects with a response (Stringent Complete Response [sCR], Complete Response [CR], Very Good Partial Response [VGPR] or Partial Response [PR]) based on the International Myeloma Working Group (IMWG) criteria.

    Measured: Cycle 2 Day 1 and Day 1 of every cycle thereafter for up to 2 years following the first dose of the last subject enrolled

  5. Cmax of ABBV-838

    Measured: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

  6. Tmax of ABBV-838

    Measured: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

  7. AUC over the dose interval (AUC0-τ) of ABBV-838

    Measured: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

  8. Total monoclonal anti-CS1 antibody (total mAb)

    Measured: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

  9. Monomethyl auristatin E (MMAE) toxin levels

    Measured: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

  10. Minimal Residual Disease (MRD)

    MRD will be assessed in the bone marrow by next generation sequencing (NGS). MRD negativity in bone marrow aspirates will be defined at 10-5 threshold as assessed by NGS.

    Measured: Cycle 4 Day 1 and treatment completion (up to 2 years following the first dose of the last subject enrolled)

  11. Terminal phase elimination rate constant (β) for ABBV-838

    Measured: Cycle 1 Day 1

  12. Terminal elimination half-life (t1/2) for ABBV-838

    Measured: Cycle 1 Day 1

Timeline

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

  1. First posted1 Nov 2016 (estimated)
  2. Study start31 Aug 2017 (estimated)
  3. Primary completion28 Jul 2020 (estimated)
  4. Study completion28 Apr 2021 (estimated)

Why it stopped: No participants enrolled

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02951117
Sponsor's protocol ID
M15-655
Other IDs
2016-001300-28, 2016
Status last verified
Jun 2017
First submitted
28 Oct 2016
Last updated
5 Jun 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax, ABBV-838 and Dexamethasone in people with Multiple Myeloma, run by AbbVie at 3 sites in Australia.

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 7 inclusion and 4 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: withdrawn, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Australia. 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 was withdrawn before enrolling participants, so there are no results.

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?

Maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of venetoclax and ABBV-838 combination therapy when administered with dexamethasone (time frame: Minimum first cycle of dosing (21 or 28 days, depending on arm)). The study lists 2 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 NCT02951117.

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 5 Jun 2017.

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