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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03360006
Recruitment Status : Recruiting
First Posted : December 2, 2017
Last Update Posted : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

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).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia (AML) Drug: ABBV-744 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABBV-744 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML)
Actual Study Start Date : March 16, 2018
Estimated Primary Completion Date : January 14, 2022
Estimated Study Completion Date : January 14, 2022


Arm Intervention/treatment
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.
Drug: ABBV-744
Tablet, oral

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




Primary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) of ABBV-744 [ Time Frame: Through Cycle 2 ( each cycle is 28 days) ]
    Cmax of ABBV-744.

  2. Time to Cmax (Tmax) of ABBV-744 [ Time Frame: Through Cycle 2 ( each cycle is 28 days) ]
    Tmax of ABBV-744.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03360006


Contacts
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Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

Locations
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United States, California
UC Irvine /ID# 160789 Recruiting
Orange, California, United States, 92868
UC Davis Comprehensive Cancer Center - Main /ID# 202729 Recruiting
Sacramento, California, United States, 95817
United States, Illinois
Northwestern /ID# 171098 Recruiting
Chicago, Illinois, United States, 60611
University of Chicago /ID# 160702 Recruiting
Chicago, Illinois, United States, 60637-1443
United States, Ohio
Cleveland Clinic Main Campus /ID# 160756 Recruiting
Cleveland, Ohio, United States, 44195
United States, Texas
University of Texas MD Anderson Cancer Center /ID# 160701 Recruiting
Houston, Texas, United States, 77030
United States, Washington
Swedish-Center for Blood Disor /ID# 166487 Recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03360006    
Other Study ID Numbers: M16-415
First Posted: December 2, 2017    Key Record Dates
Last Update Posted: June 9, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by AbbVie:
Acute Myeloid Leukemia (AML)
Relapsed/refractory acute myeloid leukemia
Dose-limiting toxicity
Recommended phase two dose
Pharmacokinetics
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms