A Study Evaluating the Safety and Pharmacokinetics of ABBV-744 in Participants With Relapsed/Refractory Acute Myeloid Leukemia (AML) Cancer

A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABBV-744 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML)

This is an open-label, Phase 1, dose-escalation (Segment 1) and expansion (Segment 2) study to determine the maximum tolerated dose (MTD) and/or the recommended phase two dose (RPTD), and to assess the safety, preliminary efficacy, and pharmacokinetic (PK) profile of ABBV-744 in participants with relapsed/refractory Acute Myeloid Leukemia (AML).

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: ABBV-744

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • UC Irvine /ID# 160789
    • Sacramento, California, United States, 95817
      • University of California, Davis Comprehensive Cancer Center /ID# 202729
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern /ID# 171098
    • Chicago, Illinois, United States, 60637-1443
      • University of Chicago DCAM /ID# 160702
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus /ID# 160756
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center /ID# 160701
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish-Center for Blood Disor /ID# 166487

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant must have AML not amenable to curative therapy, refractory to standard of care therapy or for which standard of care therapy does not exist. Participants who are candidates for stem cell transplantation must have been offered this therapeutic option.
• Must consent to provide biomarker analyses as described in the protocol.

• Must have an Eastern Cooperative Oncology Group (ECOG) Performance status of:

  • Dose Escalation (Segment 1): 0 - 1
  • Dose Expansion (Segment 2): 0 - 2
• Dose Escalation: Must have a serum albumin during Screening of >= 3.0 g/dL.
• Participant has adequate bone marrow, renal and hepatic function.

Exclusion Criteria:

• Participant with known active Central Nervous System (CNS) disease.
• Participant has received anti-cancer traditional medicine or anti-cancer herbal remedies within 14 days prior to ABBV-744 dosing. Saw palmetto is considered anti-cancer herbal remedy. Participant has received anti-cancer therapy within a period of 14 days or 5 half-lives (whichever is longer; except for immunotherapy where a period of 21 days will be acceptable) prior to Study Day 1. Except for hydroxyurea which will be allowed during screening and treatment for controlling leukocytosis.
• Participant has been previously treated with a Bromodomain and Extra-Terminal (BET) inhibitor
• Participant has unresolved clinically significant toxicities from most recent prior anti-cancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE v 4.03) grade 2 or higher clinically significant toxicity (excluding alopecia).
• Participant has received the following within 7 days prior to the first dose of study drug: corticosteroid therapy, CYP3A inhibitors, CYP3A inducers.
• Participant consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug.
• Participant had major surgery within 28 days prior to Study Day 1.
• Participant is unable to swallow or absorb oral tablets.
• Participant has known infection with hepatitis B or hepatitis C.
• Participant has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis, enteritis, colitis.
• Participant has symptoms of gross hematuria or gross hemoptysis
• Has electrocardiogram with a QT interval corrected for heart rate using Fridericia's formula (QTcF) > 470 msec or ECG with second degree type 2 or third degree atrioventricular block.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABBV-744 Dose Escalation; ABBV-744 will be administered at escalating dose levels until the maximum tolerated dose is reached and a recommended Phase 2 dose is determined.	Drug: ABBV-744; Tablet, oral
Experimental: ABBV-744 Dose Expansion; ABBV-744 will be administered at the recommended Phase 2 dose determined during the Dose Escalation phase.	Drug: ABBV-744; Tablet, oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax) of ABBV-744	Cmax of ABBV-744.	Through Cycle 2 ( each cycle is 28 days)
Time to Cmax (Tmax) of ABBV-744	Tmax of ABBV-744.	Through Cycle 2 ( each cycle is 28 days)
Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt) of ABBV-744	Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt) of ABBV-744.	Through Cycle 2 ( each cycle is 28 days)
Terminal Phase Elimination Rate Constant (β) of ABBV-744	Terminal Phase Elimination Rate Constant (β) of ABBV-744.	Through Cycle 2 ( each cycle is 28 days)
Area under the plasma concentration-time curve (AUC) from time 0 to infinity (AUCinf) of ABBV-744	Area under the plasma concentration-time curve (AUC) from time 0 to infinity (AUCinf) of ABBV-744.	Through Cycle 2 ( each cycle is 28 days)
Dose-limiting toxicity (DLT) of ABBV-744	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications and occurring during the first 4 weeks after administration of the first dose and that meets additional criteria as described in the protocol.	Up to 28 days after first dose of study drug
Maximum Tolerated Dose (MTD) for ABBV-744	The MTD is defined as the highest dose for which the estimated posterior mean DLT rate is <= 33% and excessive toxicity probability is limited to maximum of 25% during the first 28 days.	Up to 28 days after first dose of study drug
Recommended Phase 2 Dose (RPTD) for ABBV-744	RPTD will be determined from a review available safety, pharmacokinetic, and efficacy data during the dose escalation phase (Segment 1) of the study.	Up to 28 days after first dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite complete remission (CRc)	Percentage of participants who achieve composite complete remission (CRc), comprised of complete remission (CR) + CR with incomplete blood count recovery (CRi) is based on the International Working Group (IWG) criteria and European Leukemia Net criteria.	Up to 2 years
Complete Remission (CR) + CR with partial hematologic recovery (CRh)	Percentage of participants who achieve CR + CR with partial hematologic recovery (CRh) is based on the International Working Group (IWG) criteria and European Leukemia Net criteria.	Up to 2 years
Objective Response Rate (ORR)	Percentage of participants who achieve ORR [composite complete remission (CRc) + Partial remission (PR)] is based on the International Working Group (IWG) criteria (CRc, PR) and European Leukemia Net criteria.	Up to 2 years
Duration of Response (DOR)	DOR is defined as the number of days from the date of first response to the first occurrence of progression or death from any cause, whichever occurs first.	Up to 2 years
Event-free survival (EFS)	Percentage of participants who achieve EFS, where EFS is defined as the date of first dose of study drug to the date of primary refractory disease, relapse from CR or CRi, or death from any cause.	Up to 2 years

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Zhang L, Cai T, Lin X, Huang X, Bui MH, Plotnik JP, Bellin RJ, Faivre EJ, Kuruvilla VM, Lam LT, Lu X, Zha Z, Feng W, Hessler P, Uziel T, Zhang Q, Cavazos A, Han L, Ferguson DC, Mehta G, Shanmugavelandy SS, Magoc TJ, Rowe J, Goodwin NC, Dorritie KA, Boyiadzis M, Albert DH, McDaniel KF, Kati WM, Konopleva M, Shen Y. Selective Inhibition of the Second Bromodomain of BET Family Proteins Results in Robust Antitumor Activity in Preclinical Models of Acute Myeloid Leukemia. Mol Cancer Ther. 2021 Oct;20(10):1809-1819. doi: 10.1158/1535-7163.MCT-21-0029. Epub 2021 Jul 12.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2018
• Primary Completion (Actual): December 19, 2020
• Study Completion (Actual): December 19, 2020

Study Registration Dates

• First Submitted: November 28, 2017
• First Submitted That Met QC Criteria: November 28, 2017
• First Posted (Actual): December 2, 2017

Study Record Updates

• Last Update Posted (Actual): March 24, 2021
• Last Update Submitted That Met QC Criteria: March 22, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Acute Myeloid Leukemia (AML); Relapsed/refractory acute myeloid leukemia; Dose-limiting toxicity; Recommended phase two dose
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: M16-415

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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