Back to resultsA Study Evaluating the Safety and Pharmacokinetics of ABBV-744 in Participants With Relapsed/Refractory Acute Myeloid Leukemia (AML) Cancer
Primary Purpose
Acute Myeloid Leukemia (AML)
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ABBV-744
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring Acute Myeloid Leukemia (AML), Relapsed/refractory acute myeloid leukemia, Dose-limiting toxicity, Recommended phase two dose, Pharmacokinetics
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.
Sites / Locations
- UC Irvine /ID# 160789
- University of California, Davis Comprehensive Cancer Center /ID# 202729
- Northwestern /ID# 171098
- University of Chicago DCAM /ID# 160702
- Cleveland Clinic Main Campus /ID# 160756
- University of Texas MD Anderson Cancer Center /ID# 160701
- Swedish-Center for Blood Disor /ID# 166487
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ABBV-744 Dose Escalation
ABBV-744 Dose Expansion
Arm Description
ABBV-744 will be administered at escalating dose levels until the maximum tolerated dose is reached and a recommended Phase 2 dose is determined.
ABBV-744 will be administered at the recommended Phase 2 dose determined during the Dose Escalation phase.
Outcomes
Primary Outcome Measures
Maximum observed plasma concentration (Cmax) of ABBV-744
Cmax of ABBV-744.
Time to Cmax (Tmax) of ABBV-744
Tmax 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
Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt) of ABBV-744.
Terminal Phase Elimination Rate Constant (β) of ABBV-744
Terminal Phase Elimination Rate Constant (β) of ABBV-744.
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.
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03360006
Brief Title
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
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
Strategic Reasons
Study Start Date
March 16, 2018 (Actual)
Primary Completion Date
December 19, 2020 (Actual)
Study Completion Date
December 19, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML)
Keywords
Acute Myeloid Leukemia (AML), Relapsed/refractory acute myeloid leukemia, Dose-limiting toxicity, Recommended phase two dose, Pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ABBV-744 Dose Escalation
Arm Type
Experimental
Arm Description
ABBV-744 will be administered at escalating dose levels until the maximum tolerated dose is reached and a recommended Phase 2 dose is determined.
Arm Title
ABBV-744 Dose Expansion
Arm Type
Experimental
Arm Description
ABBV-744 will be administered at the recommended Phase 2 dose determined during the Dose Escalation phase.
Intervention Type
Drug
Intervention Name(s)
ABBV-744
Intervention Description
Tablet, oral
Primary Outcome Measure Information:
Title
Maximum observed plasma concentration (Cmax) of ABBV-744
Description
Cmax of ABBV-744.
Time Frame
Through Cycle 2 ( each cycle is 28 days)
Title
Time to Cmax (Tmax) of ABBV-744
Description
Tmax of ABBV-744.
Time Frame
Through Cycle 2 ( each cycle is 28 days)
Title
Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt) of ABBV-744
Description
Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt) of ABBV-744.
Time Frame
Through Cycle 2 ( each cycle is 28 days)
Title
Terminal Phase Elimination Rate Constant (β) of ABBV-744
Description
Terminal Phase Elimination Rate Constant (β) of ABBV-744.
Time Frame
Through Cycle 2 ( each cycle is 28 days)
Title
Area under the plasma concentration-time curve (AUC) from time 0 to infinity (AUCinf) of ABBV-744
Description
Area under the plasma concentration-time curve (AUC) from time 0 to infinity (AUCinf) of ABBV-744.
Time Frame
Through Cycle 2 ( each cycle is 28 days)
Title
Dose-limiting toxicity (DLT) of ABBV-744
Description
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.
Time Frame
Up to 28 days after first dose of study drug
Title
Maximum Tolerated Dose (MTD) for ABBV-744
Description
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.
Time Frame
Up to 28 days after first dose of study drug
Title
Recommended Phase 2 Dose (RPTD) for ABBV-744
Description
RPTD will be determined from a review available safety, pharmacokinetic, and efficacy data during the dose escalation phase (Segment 1) of the study.
Time Frame
Up to 28 days after first dose of study drug
Secondary Outcome Measure Information:
Title
Composite complete remission (CRc)
Description
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.
Time Frame
Up to 2 years
Title
Complete Remission (CR) + CR with partial hematologic recovery (CRh)
Description
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.
Time Frame
Up to 2 years
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
Up to 2 years
Title
Duration of Response (DOR)
Description
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.
Time Frame
Up to 2 years
Title
Event-free survival (EFS)
Description
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.
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
UC Irvine /ID# 160789
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of California, Davis Comprehensive Cancer Center /ID# 202729
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Northwestern /ID# 171098
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Chicago DCAM /ID# 160702
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1443
Country
United States
Facility Name
Cleveland Clinic Main Campus /ID# 160756
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center /ID# 160701
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Swedish-Center for Blood Disor /ID# 166487
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34253595
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.
Results Reference
derived
Learn more about this trial
A Study Evaluating the Safety and Pharmacokinetics of ABBV-744 in Participants With Relapsed/Refractory Acute Myeloid Leukemia (AML) Cancer
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