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

NCT03360006 | Terminated Phase 1 FDA Drug

• 1 other identifier: M16-415
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

Brief Summary

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).

Conditions

Acute Myeloid Leukemia (AML)

Keywords

Acute Myeloid Leukemia (AML); Relapsed/refractory acute myeloid leukemia; Dose-limiting toxicity; Recommended phase two dose; Pharmacokinetics

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (5)

• Composite complete remission (CRc)

  Up to 2 years

• Complete Remission (CR) + CR with partial hematologic recovery (CRh)

  Up to 2 years

• Objective Response Rate (ORR)

  Up to 2 years

• Duration of Response (DOR)

  Up to 2 years

• Event-free survival (EFS)

  Up to 2 years

Study Arms (2)

ABBV-744 Dose Escalation

EXPERIMENTAL

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

ABBV-744 Dose Expansion

EXPERIMENTAL

ABBV-744 will be administered at the recommended Phase 2 dose determined during the Dose Escalation phase.

Drug: ABBV-744

Interventions

ABBV-744 DRUG

Tablet, oral

ABBV-744 Dose Escalation; ABBV-744 Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (7)

UC Irvine /ID# 160789

Orange, California, 92868, United States

Location

University of California, Davis Comprehensive Cancer Center /ID# 202729

Sacramento, California, 95817, United States

Location

Northwestern /ID# 171098

Chicago, Illinois, 60611, United States

Location

University of Chicago DCAM /ID# 160702

Chicago, Illinois, 60637-1443, United States

Location

Cleveland Clinic Main Campus /ID# 160756

Cleveland, Ohio, 44195, United States

Location

University of Texas MD Anderson Cancer Center /ID# 160701

Houston, Texas, 77030, United States

Location

Swedish-Center for Blood Disor /ID# 166487

Seattle, Washington, 98104, United States

Location

Related Publications (2)

• Crymes A, Evans MG, Jeyakumar D, Lou JJ, Zhao X, Rezk SA. Acute Myeloid Leukemia (AML) With T-Cell Differentiation Arising From Chronic Myelomonocytic Leukemia (CMML). Case Rep Hematol. 2024 Dec 14;2024:5584297. doi: 10.1155/crh/5584297. eCollection 2024.

  PMID: 39734743 DERIVED

• 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.

  PMID: 34253595 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

ABBV-744

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2017
• First Posted: December 2, 2017
• Study Start: March 16, 2018
• Primary Completion: December 19, 2020
• Study Completion: December 19, 2020
• Last Updated: March 24, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)