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

• ClinicalTrials.gov Identifier: NCT03360006
• Recruitment Status: Terminated
• First Posted: December 2, 2017
• Last Update Posted: March 24, 2021
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: November 28, 2017
• First Posted Date: December 2, 2017
• Last Update Posted Date: March 24, 2021
• Actual Study Start Date: March 16, 2018
• Actual Primary Completion Date: December 19, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 3, 2020)

• Maximum observed plasma concentration (Cmax) of ABBV-744 [ Time Frame: Through Cycle 2 ( each cycle is 28 days) ]
  Cmax of ABBV-744.
• Time to Cmax (Tmax) of ABBV-744 [ Time Frame: Through Cycle 2 ( each cycle is 28 days) ]
  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 [ Time Frame: 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.
• Terminal Phase Elimination Rate Constant (β) of ABBV-744 [ Time Frame: Through Cycle 2 ( each cycle is 28 days) ]
  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 [ Time Frame: 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.
• Dose-limiting toxicity (DLT) of ABBV-744 [ Time Frame: Up to 28 days after first dose of study drug ]
  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 [ Time Frame: Up to 28 days after first dose of study drug ]
  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 [ Time Frame: Up to 28 days after first dose of study drug ]
  RPTD will be determined from a review available safety, pharmacokinetic, and efficacy data during the dose escalation phase (Segment 1) of the study.

Original Primary Outcome Measures (submitted: November 28, 2017)

• Dose-limiting toxicity (DLT) of ABBV-744 [ Time Frame: Up to 28 days after first dose of study drug ]
  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 [ Time Frame: Up to 28 days after first dose of study drug ]
  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 [ Time Frame: Up to 28 days after first dose of study drug ]
  RPTD will be determined from a review available safety, pharmacokinetic, and efficacy data during the dose escalation phase (Segment 1) of the study.
• Cmax of ABBV-744 [ Time Frame: Up to 16 days after first dose of study drug in dose-escalation phase only ]
  Maximum observed plasma concentration (Cmax) of ABBV-744
• Time of ABBV-744 [ Time Frame: Up to 16 days after first dose of study drug in dose-escalation phase only ]
  Time to Cmax (Tmax) of ABBV-744
• AUCt of ABBV-744 [ Time Frame: Up to 16 days after first dose of study drug in dose-escalation phase only ]
  Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt) of ABBV-744

Current Secondary Outcome Measures (submitted: April 3, 2020)

• Composite complete remission (CRc) [ Time Frame: Up to 2 years ]
  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) [ Time Frame: Up to 2 years ]
  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) [ Time Frame: Up to 2 years ]
  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) [ Time Frame: Up to 2 years ]
  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) [ Time Frame: Up to 2 years ]
  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.

Original Secondary Outcome Measures (submitted: November 28, 2017)

• Radiographic Progression Free Survival (rPFS) for CRPC [ Time Frame: Up to 2 years ]
  Percentage of participants who achieve rPFS where rPFS is describer per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Prostate Cancer Working Group 3 (PCWG3) criteria.
• Time to Disease Progression (TTP) for CRPC [ Time Frame: Up to 2 years ]
  TTP is calculated as number of days from the date the participant started study drug to date of disease progression as confirmed per RECIST 1.1 and/or PCWG3 criteria.
• Time to Prostate-specific Antigen (PSA) Progression for CRPC [ Time Frame: Up to 2 years ]
  Time to PSA Progression is defined as the number of days from the date the participant started study drug to time of confirmed PSA progression as defined by PCGW3.
• Duration of Response (DOR) for CRPC [ Time Frame: Up to 2 years ]
  Percentage of participants who achieve DOR where DOR is defined as the number of days from the day the response criteria are met to the date that disease progression is objectively documented.
• Objective Response Rate (ORR) for CRPC [ Time Frame: Up to 2 years ]
  Percentage of participants who achieve ORR where ORR is based on RECIST 1.1 criteria (partial response or complete response).
• Overall PSA Response Rate for CRPC [ Time Frame: Up to 2 years ]
  Overall PSA response rate per PCWG3 criteria.
• Progression-free survival (PFS) for Acute Myeloid Leukemia (AML) [ Time Frame: Up to 2 years ]
  Percentage of participants who achieve progression-free survival (PFS) where PFS is defined as the number of days from the date the participant started study drug to the date of the participants disease progression or death due to any cause, whichever occurs first.
• ORR for AML [ Time Frame: Up to 2 years ]
  Percentage of participants who achieve where ORR for AML participants is based on the International Working Group (IWG) criteria (complete remission, complete remission with incomplete blood count recovery, partial remission, morphologic leukemia free state).
• DOR for AML [ Time Frame: Up to 2 years ]
  DOR is defined as the number of days from the day the response criteria are met to the date that disease progression is objectively documented

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia (AML)

Intervention

Drug: ABBV-744

Tablet, oral

Study Arms

• 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.
  Intervention: Drug: ABBV-744
• Experimental: ABBV-744 Dose Expansion
  ABBV-744 will be administered at the recommended Phase 2 dose determined during the Dose Escalation phase.
  Intervention: Drug: ABBV-744

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 22, 2021): 30
• Original Estimated Enrollment (submitted: November 28, 2017): 80
• Actual Study Completion Date: December 19, 2020
• Actual Primary Completion Date: December 19, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03360006
• Other Study ID Numbers: M16-415
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: March 2021