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

Acute Myeloid Leukemia (AML) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03360006
• Other study ID #: M16-415
• Status: Terminated
• Phase: Phase 1
• Start date: March 16, 2018
• Est. completion date: December 19, 2020

Study information

• Verified date: March 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: December 19, 2020
• Est. primary completion date: December 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• ABBV-744
Tablet, oral

Locations

Country	Name	City	State
United States	Northwestern /ID# 171098	Chicago	Illinois
United States	University of Chicago DCAM /ID# 160702	Chicago	Illinois
United States	Cleveland Clinic Main Campus /ID# 160756	Cleveland	Ohio
United States	University of Texas MD Anderson Cancer Center /ID# 160701	Houston	Texas
United States	UC Irvine /ID# 160789	Orange	California
United States	University of California, Davis Comprehensive Cancer Center /ID# 202729	Sacramento	California
United States	Swedish-Center for Blood Disor /ID# 166487	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed plasma concentration (Cmax) of ABBV-744	Cmax of ABBV-744.	Through Cycle 2 ( each cycle is 28 days)
Primary	Time to Cmax (Tmax) of ABBV-744	Tmax of ABBV-744.	Through Cycle 2 ( each cycle is 28 days)
Primary	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)
Primary	Terminal Phase Elimination Rate Constant (ß) of ABBV-744	Terminal Phase Elimination Rate Constant (ß) of ABBV-744.	Through Cycle 2 ( each cycle is 28 days)
Primary	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)
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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