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A Study of the Safety and Tolerability of ABBV-621 in Participants With Previously Treated Solid Tumors and Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT03082209
Recruitment Status : Recruiting
First Posted : March 17, 2017
Last Update Posted : April 3, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:
This is an open-label, Phase I, dose-escalation study to determine the maximum tolerated dose (MTD) and/or recommended phase two dose (RPTD), and evaluate the safety, efficacy, and pharmacokinetic (PK) profile of ABBV-621 for participants with previously treated solid tumors or hematologic malignancies. The study will consist of 2 segments: Segment I (Dose Escalation for Solid Tumors) and Segment II (Dose Expansion for Solid Tumors; RPTD confirmation for Acute Myeloid Leukemia [AML]; combination with venetoclax for AML and Diffuse Large B-Cell Lymphoma [DLBCL]).

Condition or disease Intervention/treatment Phase
Solid Tumors Hematologic Malignancies Drug: ABBV-621 Drug: Venetoclax Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 1, First-In-Human Study of Safety and Tolerability of TRAIL Receptor Agonist ABBV-621 in Subjects With Previously Treated Solid Tumors and Hematologic Malignancies
Actual Study Start Date : April 3, 2017
Estimated Primary Completion Date : November 16, 2018
Estimated Study Completion Date : May 24, 2020


Arm Intervention/treatment
Experimental: Segment I: Dose Escalation
ABBV-621 via intravenous administration at escalating dose levels in participants with solid tumors including Non-Hodgkin Lymphoma (NHL).
Drug: ABBV-621
Intravenous
Experimental: Segment II: Expansion Cohort for Advanced Solid Tumors
Participants with solid tumors will be treated with single-agent ABBV-621 at the recommended Phase 2 dose (RP2D).
Drug: ABBV-621
Intravenous
Experimental: Segment II: Expansion Cohort for CRC
Participants with colorectal cancer (CRC) will be treated with single-agent ABBV-621 at the RP2D.
Drug: ABBV-621
Intravenous
Experimental: Segment II: ABBV-621 + Venetoclax for DLBCL
Participants with diffuse large B-cell lymphoma (DLBCL) will be treated with a combination of ABBV-621 and venetoclax.
Drug: ABBV-621
Intravenous
Drug: Venetoclax
tablet, oral
Other Names:
  • ABT-199
  • GDC-0199
Experimental: Segment II: ABBV-621 Monotherapy for AML
Participants with Acute Myeloid Leukemia (AML) will commence ABBV-621 monotherapy via intravenous administration at the RP2D (per Segment I); dose escalation will progress until RP2D is determined for AML participants.
Drug: ABBV-621
Intravenous
Experimental: Segment II: ABBV-621 + Venetoclax for AML
Additional participants with AML will be enrolled and will be treated with a combination of ABBV-621 and venetoclax.
Drug: ABBV-621
Intravenous
Drug: Venetoclax
tablet, oral
Other Names:
  • ABT-199
  • GDC-0199



Primary Outcome Measures :
  1. Segment I: Area under the serum concentration time curve (AUC) of ABBV-621 [ Time Frame: Up to 64 days ]
    Area under the serum concentration time curve (AUC) of ABBV-621.

  2. Segment I: Maximum observed serum concentration (Cmax) of ABBV-621 [ Time Frame: Up to 64 days ]
    Maximum observed serum concentration (Cmax) of ABBV-621.

  3. Segment I: Terminal phase elimination rate constant (β) [ Time Frame: Up to 64 days ]
    Terminal phase elimination rate constant (β).

  4. Segment II: Response Rate in Solid Tumors, DLBCL, AML and NHL [ Time Frame: Approximately 6 months ]
    Response rate defined as the proportion of participants with a response of partial response (PR) or better per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for colorectal cancer (CRC) and other solid tumor participants, or per the Complete Response (CR) with incomplete blood count recovery (CRi) or better (composite of CR + CRi) per the modified International Working Group (IWG) criteria for Acute Myeloid Leukemia (AML) participants, or PR or better per the Lugano response criteria for Non-Hodgkin Lymphoma (NHL) participants.

  5. Segment I: Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) for ABBV-621 [ Time Frame: Up to 21 days ]
    The MTD and/or RP2D of ABBV-621 will be determined during the dose escalation phase (Segment I) of the study of ABBV-621 in participants with solid tumors (including NHL).

  6. Segment I: Time to Cmax (Tmax) of ABBV-621 [ Time Frame: Up to 64 days ]
    Time to Cmax (Tmax) of ABBV-621.


Secondary Outcome Measures :
  1. Segment I: QTcF Change from Baseline [ Time Frame: Up to 64 days ]
    QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline by dose level

  2. Number of Participants with Dose-limiting Toxicities (DLTs) [ Time Frame: Up to 42 days after first day of study drug administration or 14 days after bone marrow biopsy showing < 5% blast count (whichever is later) ]
    Dose limiting toxicities for dose escalation purposes will be determined on events that occur during the first 21-day cycle (with protocol specified exceptions for AML participants).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have a diagnosis of a solid tumor (except primary brain tumors), acute myeloid leukemia (AML), or non-Hodgkin lymphoma (NHL); NHL may be of any subtype for Segment I but must be diffuse large B-cell lymphoma (DLBCL) for Segment II.
  • Must have received at least one prior systemic therapy, and must have relapsed or progressed after, or failed to respond to any/all available effective therapy or therapies.
  • Must have measurable disease (by Response Evaluation Criteria In Solid Tumors [RECIST] 1.1 for those with solid tumors; by Lugano classification for those with NHL), except those with AML, who must have histologically confirmed relapsed or refractory disease.
  • Must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 - 2.
  • Must have adequate hematologic, renal and hepatic function.

Exclusion Criteria:

  • Participants with history of brain metastases who have not shown clinical and radiographic stable disease for at least 28 days after definitive therapy.
  • Presence of primary hepatobiliary malignancy, including cholangiocarcinoma or hepatocellular carcinoma, gallbladder carcinoma, cancer of ampulla of Vater.
  • Receipt of any systemic anti-cancer agent, including investigational anti-cancer products, within 21 days prior to study drug administration or 3 half-lives, whichever is longer.
  • Participant with a history of cirrhosis or other indication of significant possible hepatic dysfunction. Note: Those with non-alcoholic steatohepatitis (NASH) should be discussed with the AbbVie TA MD before enrollment.
  • Participant with a positive diagnosis of hepatitis A, B, or C.

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): NCT03082209


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

Locations
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06510
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637-1443
Ingalls Not yet recruiting
Harvey, Illinois, United States, 60426
United States, Rhode Island
The Warren Alpert Medical Scho Not yet recruiting
Providence, Rhode Island, United States, 02903
United States, Texas
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
United States, Wisconsin
Medical College of Wisconsin Not yet recruiting
Milwaukee, Wisconsin, United States, 53226-3522
Japan
National Cancer Ctr Hosp East Recruiting
Kashiwa-shi, Chiba, Japan, 277-8577
Netherlands
UMCG Not yet recruiting
Groningen, Netherlands, 9700 RB
Erasmus Medisch Centrum Recruiting
Rotterdam, Netherlands, 3015 CE
UMC Utrecht Not yet recruiting
Utrecht, Netherlands, 3584 CX
Spain
Hospital General Vall D'Hebron Not yet recruiting
Barcelona, Spain, 08035
Hospital Fundacion Jimenez Dia Not yet recruiting
Madrid, Spain, 28040
Hosp Univ Madrid Sanchinarro Recruiting
Madrid, Spain, 28050
Sponsors and Collaborators
AbbVie
Investigators
Study Director: AbbVie Inc. AbbVie

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03082209     History of Changes
Other Study ID Numbers: M15-913
2016-003887-37 ( EudraCT Number )
First Posted: March 17, 2017    Key Record Dates
Last Update Posted: April 3, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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:
Solid Tumors
Hematologic Malignancies
Cancer
non-Hodgkin lymphoma
acute myeloid leukemia (AML)
colorectal cancer (CRC)
Diffuse Large B-Cell Lymphoma (DLBCL)

Additional relevant MeSH terms:
Neoplasms
Venetoclax
Antineoplastic Agents