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Trial record 1 of 1 for:    NCT04445701
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Study of AO-176 as Monotherapy and in Combination With Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04445701
Recruitment Status : Not yet recruiting
First Posted : June 24, 2020
Last Update Posted : June 24, 2020
Sponsor:
Information provided by (Responsible Party):
Arch Oncology

Tracking Information
First Submitted Date  ICMJE June 17, 2020
First Posted Date  ICMJE June 24, 2020
Last Update Posted Date June 24, 2020
Estimated Study Start Date  ICMJE July 2020
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2020)
  • Phase 1: MTD / RP2D of AO-176 assessed by incidence of dose-limiting toxicities and incidence of treatment-related adverse events (TEAEs) as assessed by CTCAE v5.0 [ Time Frame: 12 months ]
    Safety and tolerability of AO-176 when administered as monotherapy and in combination with dexamethasone or with dexamethasone plus bortezomib in adult patients with R/R MM as assessed by incidence of DLTs and TEAEs as assessed by CTCAE v5.0
  • Phase 2: Objective response rate (ORR) of AO-176 + DEX + BORT [ Time Frame: 12 months ]
    Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on ORR using International Myeloma Working Group (IMWG) uniform response criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2020)
  • Phase 1: ORR of single agent AO-176 [ Time Frame: 12 months ]
    Evaluate the clinical activity of single agent AO-176 based on ORR using IMWG uniform response criteria
  • Phase 1: Duration of response (DOR) of single agent AO-176 [ Time Frame: 12 months ]
    Evaluate the clinical activity of single agent AO-176 based on DOR using IMWG uniform response criteria
  • Phase 1: Disease control rate (DCR) of single agent AO-176 [ Time Frame: 12 months ]
    Evaluate the clinical activity of single agent AO-176 based on DCR using IMWG uniform response criteria
  • Phase 1: Progression-free survival (PFS) of single agent AO-176 [ Time Frame: 12 months ]
    Evaluate the clinical activity of single agent AO-176 based on PFS using IMWG uniform response criteria
  • Phase 1: Overall survival (OS) of single agent AO-176 [ Time Frame: 12 months ]
    Evaluate the clinical activity of single agent AO-176 based on OS
  • Phase 2: DOR of AO-176 + DEX + BORT [ Time Frame: 12 months ]
    Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on DOR using IMWG uniform response criteria
  • Phase 2: DCR of AO-176 + DEX + BORT [ Time Frame: 12 months ]
    Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on DCR using IMWG uniform response criteria
  • Phase 2: PFS of AO-176 + DEX + BORT [ Time Frame: 12 months ]
    Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on PFS using IMWG uniform response criteria
  • Phase 2: OS of AO-176 + DEX + BORT [ Time Frame: 12 months ]
    Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on OS
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of AO-176 as Monotherapy and in Combination With Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma
Official Title  ICMJE A Phase 1/2, Dose Escalation Safety and Tolerability Study of AO-176 as Monotherapy and in Combination With Bortezomib and Dexamethasone in Adults With Relapsed or Refractory Multiple Myeloma
Brief Summary Open-label, dose escalation study to evaluate the safety, tolerability, pharmacokinetics (PK)/pharmacodynamics and initial efficacy of AO-176 as monotherapy and in combination with dexamethasone and bortezomib in adults with relapsed/refractory multiple myeloma (MM).
Detailed Description

An open-label, multicenter, dose escalation study to evaluate the safety, tolerability and PK/pharmacodynamics of AO-176 in adults with relapsed/refractory multiple myeloma whose disease has progressed following at least 3 prior systemic lines of treatment and must have progressed on the final line of therapy received before being considered for this study.

The study will be conducted in 2 phases; Phase 1 is an ascending-dose study of AO-176 monotherapy utilizing the classic 3+3 design, with enrollment of 3 patients per cohort and expansion of the cohort in the event of a dose-limiting toxicity (DLT). Following the dose escalation portion and determination of the monotherapy recommended phase 2 dose (RP2D), an ascending dose escalation study of AO-176 and dexamethasone combined with bortezomib will be evaluated utilizing the same 3+3 dose escalation design.

Phase 2 will evaluate the clinical activity of AO-176 plus dexamethasone and bortezomib at the RP2D as determined in Phase 1 Part 2.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Phase 1 Part 1: Up to 4 dose escalation cohorts will be enrolled; each cohort will initially recruit 3 patients to receive AO-176 monotherapy in a standard 3+3 design; the cohort will be expanded in the event of a DLT. Once the RP2D has been identified, an expansion cohort will be enrolled to evaluate AO-176 at the RP2D in combination with dexamethasone (DEX).

Phase 1 Part 2: Dose escalation cohorts will evaluate AO-176 in combination with DEX and bortezomib (BORT) to determine the RP2D of AO-176 + DEX + BORT in a standard 3+3 design; the cohort will be expanded in the event of a DLT.

Phase 2: Up to 48 patients will be enrolled to evaluate the preliminary efficacy of AO-176 + DEX + BORT using a Simon 2-stage design.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: AO-176
    Humanized monoclonal antibody (mAb) targeting CD47
  • Drug: AO-176 + Dex
    Humanized mAb targeting CD47 plus dexamethasone
  • Drug: AO-176 + Dex + Bort
    Humanized mAb targeting CD47 plus dexamethasone plus bortezomib
Study Arms  ICMJE
  • Experimental: AO-176 Dose Escalation Monotherapy
    The dose escalation monotherapy cohorts will initially recruit 3 patients to receive AO-176 in a standard 3+3 design; cohorts will be expanded in the event of a DLT.
    Intervention: Drug: AO-176
  • Experimental: AO-176 + DEX Expansion Cohort
    Once the monotherapy RP2D has been established, an expansion cohort of AO-176 + dexamethasone will be enrolled.
    Intervention: Drug: AO-176 + Dex
  • Experimental: AO-176 + DEX + BORT Dose Escalation
    Following evaluation of AO-176 + dexamethasone, dose escalation cohorts of AO-176 + dexamethasone + bortezomib will be enrolled. Each dose escalation cohort will initially recruit 3 patients in a standard 3+3 design; cohorts will be expanded in the event of a DLT. The Phase 2 portion of the study will further evaluate the RP2D of AO-176 + DEX + BORT.
    Intervention: Drug: AO-176 + Dex + Bort
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 22, 2020)
102
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Confirmed diagnosis of symptomatic MM per IMWG criteria
  2. Measurable disease
  3. Relapsed or refractory to at least 3 prior systemic lines of therapy for MM
  4. Eastern Cooperative Oncology Group (ECOG) status 0-1
  5. Resolution of prior therapy-related adverse events
  6. Minimum of 2 weeks since last dose of cancer therapy or radiotherapy

Key Exclusion Criteria:

  1. Previous Grade 3-4 infusion or hypersensitivity reaction
  2. Severe asthma or chronic obstructive pulmonary disease exacerbations requiring hospital admission or steroids
  3. Prior treatment with a checkpoint inhibitor (anti-PD-1, PD-L1 or CTLA-4) within 4 weeks.
  4. Prior treatment with a therapeutic agent that targets the CD47 axis.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kevin Romanko, DPM 415-671-4028 kromanko@archoncology.com
Contact: Amy Douglas adouglas@archoncology.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04445701
Other Study ID Numbers  ICMJE AO-176-102
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Arch Oncology
Study Sponsor  ICMJE Arch Oncology
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jackie Walling, MBChB, PhD Arch Oncology
PRS Account Arch Oncology
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP