Clinical trial NCT03360006: A Study Evaluating the Safety and Pharmacokinetics of ABBV-744 in Participants With Relapsed/Refractory Acute Myeloid Leukemia (AML) Cancer
Official title: A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABBV-744 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia (AML)
Keywords: Acute Myeloid Leukemia (AML)
Relapsed/refractory acute myeloid leukemia
Dose-limiting toxicity
Recommended phase two dose
Pharmacokinetics
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2017-12-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax) of ABBV-744
timeFrame: Through Cycle 2 ( each cycle is 28 days)
measure: Time to Cmax (Tmax) of ABBV-744
timeFrame: Through Cycle 2 ( each cycle is 28 days)
measure: Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt) of ABBV-744
timeFrame: Through Cycle 2 ( each cycle is 28 days)
measure: Terminal Phase Elimination Rate Constant (β) of ABBV-744
timeFrame: Through Cycle 2 ( each cycle is 28 days)
measure: Area under the plasma concentration-time curve (AUC) from time 0 to infinity (AUCinf) of ABBV-744
timeFrame: Through Cycle 2 ( each cycle is 28 days)
measure: Dose-limiting toxicity (DLT) of ABBV-744
timeFrame: Up to 28 days after first dose of study drug
measure: Maximum Tolerated Dose (MTD) for ABBV-744
timeFrame: Up to 28 days after first dose of study drug
measure: Recommended Phase 2 Dose (RPTD) for ABBV-744
timeFrame: Up to 28 days after first dose of study drug
Secondary outcomes:
measure: Composite complete remission (CRc)
timeFrame: Up to 2 years
measure: Complete Remission (CR) + CR with partial hematologic recovery (CRh)
timeFrame: Up to 2 years
measure: Objective Response Rate (ORR)
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Event-free survival (EFS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: UC Irvine /ID# 160789
state: California
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center /ID# 202729
state: California
city: Chicago
country: United States
facility: Northwestern /ID# 171098
state: Illinois
city: Chicago
country: United States
facility: University of Chicago DCAM /ID# 160702
state: Illinois
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus /ID# 160756
state: Ohio
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center /ID# 160701
state: Texas
city: Seattle
country: United States
facility: Swedish-Center for Blood Disor /ID# 166487
state: Washington
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.