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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

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ClinicalTrials.gov Identifier: NCT02951117
Recruitment Status : Withdrawn (No participants enrolled)
First Posted : November 1, 2016
Last Update Posted : June 5, 2017
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Description
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Brief 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). 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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Venetoclax Drug: ABBV-838 Drug: Dexamethasone Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : August 31, 2017
Estimated Primary Completion Date : July 28, 2020
Estimated Study Completion Date : April 28, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A Venetoclax QD + ABBV-838 Q3W + Dexamethasone
ABBV-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.
 Drug: Venetoclax
Tablet
Other Name: ABT-199

Drug: ABBV-838
Intravenous infusion

Drug: Dexamethasone
Tablet or intravenous infusion
Experimental: Arm B Venetoclax QD + ABBV-838 Q1W or Q2W + Dexamethasone Q1W

Dose 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.

 Drug: Venetoclax
Tablet
Other Name: ABT-199

Drug: ABBV-838
Intravenous infusion

Drug: Dexamethasone
Tablet or intravenous infusion


Outcome Measures
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Primary Outcome Measures :
  1. 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 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.

  2. Number of participants with adverse events [ Time Frame: Up to approximately 2 years following the first dose of the last subject enrolled ]

Secondary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) of venetoclax [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  2. Time to Cmax (Tmax) of venetoclax [ Time Frame: 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 [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  4. Objective Response Rate (ORR) [ Time Frame: 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 ]
    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.

  5. Cmax of ABBV-838 [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  6. Tmax of ABBV-838 [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  7. AUC over the dose interval (AUC0-τ) of ABBV-838 [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  8. Total monoclonal anti-CS1 antibody (total mAb) [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  9. Monomethyl auristatin E (MMAE) toxin levels [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  10. Minimal Residual Disease (MRD) [ Time Frame: Cycle 4 Day 1 and treatment completion (up to 2 years following the first dose of the last subject enrolled) ]
    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.

  11. Terminal phase elimination rate constant (β) for ABBV-838 [ Time Frame: Cycle 1 Day 1 ]
  12. Terminal elimination half-life (t1/2) for ABBV-838 [ Time Frame: Cycle 1 Day 1 ]

Eligibility Criteria
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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 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.

Exclusion Criteria:

  • 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.
Contacts and Locations
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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): NCT02951117


Locations
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Australia
St Vincent´s Hospital /ID# 153022
Darlinghurst, Australia, 2010
St. Vincents Hospital Melbourne /ID# 157925
Fitzroy, Australia, 3065
The Alfred Hospital /ID# 150202
Prahran, Australia, 3181
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: Orlando Bueno, MD AbbVie
More Information
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02951117    
Other Study ID Numbers: M15-655
2016-001300-28 ( EudraCT Number )
First Posted: November 1, 2016    Key Record Dates
Last Update Posted: June 5, 2017
Last Verified: June 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AbbVie:
lymphoid malignancies
Next generation sequencing
Refractory Multiple Myeloma
Relapsed 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
Venetoclax
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