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Trial record 41 of 47 for:    Venetoclax AND cell lymphoma

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 : August 15, 2019
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.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 205 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 TRAIL Receptor Agonist ABBV-621 in Subjects With Previously Treated Solid Tumors and Hematologic Malignancies
Actual Study Start Date : March 20, 2017
Estimated Primary Completion Date : February 2, 2021
Estimated Study Completion Date : December 2, 2021


Arm Intervention/treatment
Experimental: 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 (IV)

Experimental: Dose Optimization for KRAS-mutant CRC
Participants with colorectal cancer (CRC) will be treated with single-agent ABBV-621 to enable selection of the RP2D.
Drug: ABBV-621
Intravenous (IV)

Experimental: Dose Optimization for Pancreatic Cancer
Participants with pancreatic cancer will be treated with single-agent ABBV-621 to enable selection of the recommended Phase 2 dose (RP2D).
Drug: ABBV-621
Intravenous (IV)

Experimental: Dose Optimization: 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 (IV)

Drug: Venetoclax
tablet, oral
Other Names:
  • ABT-199
  • GDC-0199

Experimental: Dose Optimization: ABBV-621 Monotherapy for AML
Participants with Acute Myeloid Leukemia (AML) will be treated with ABBV-621 monotherapy.
Drug: ABBV-621
Intravenous (IV)

Experimental: Dose Optimization: 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 (IV)

Drug: Venetoclax
tablet, oral
Other Names:
  • ABT-199
  • GDC-0199

Experimental: Chemotherapy combination: ABBV-621+FOLFIRI
Participants with RAS-mutant CRC who have received one prior line of therapy will be administered ABBV-621 in combination with FOLFIRI.
Drug: ABBV-621
Intravenous (IV)

Drug: FOLFIRI
IV infusion

Experimental: Chemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab
Participants with KRAS-mutant CRC are administered with ABBV-621 in combination with bevacizumab plus FOLFIRI
Drug: ABBV-621
Intravenous (IV)

Drug: Bevacizumab
IV infusion

Drug: FOLFIRI
IV infusion




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

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

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

  4. 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 of the study of ABBV-621

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


Secondary Outcome Measures :
  1. 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, Older Adult)
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 Dose Escalation but is limited to diffuse large B-cell lymphoma (DLBCL) for those enrolled to the cohort evaluating the combination of ABBV-621 and venetoclax. Participants in the Dose Optimization solid tumor cohorts must have either colorectal cancer with documented KRAS mutations (as determined by local testing), or pancreatic cancer (irrespective of mutational status). Participants in the chemotherapy combination cohorts must have metastatic or advanced unresectable colorectal cancer with documented RAS mutations (as determined by local testing).
  • Participant in dose escalation or dose optimization cohort 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.
  • Participant in chemotherapy cohorts with CRC must have progressed after or failed to respond to initial systemic therapy.
  • 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 agree to provide the following samples for biomarker analysis:

    • All participants: archived tumor tissue (if available).
    • Participants in Dose Optimization (excluding AML): pre- and on-treatment fresh tissue biopsies. (Note: fresh tissue biopsies will be optional for participants with solid tumor or NHL in Dose Escalation and will be collected only if consent is provided)
    • All participants with AML: pre- and on-treatment bone marrow aspirates (BMA)
    • Participants in chemotherapy combination cohorts: participants must provide a fresh biopsy if an archival biopsy is not available
  • Must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 - 2. Participants in chemotherapy combination cohorts must have ECOG Performance Score of 0 - 1.
  • 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. In addition, any AML participant identified through cerebrospinal fluid (CSF) analysis, as having active central nervous system (CNS) disease, will be excluded.
  • 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.
  • Dose Optimization combination cohorts only: Prior receipt, at any time, of a BCL-2 inhibitor
  • Dose Optimization combination cohorts only: Receipt of strong or moderate CYP3A inducers within 7 days prior to start of study treatment or strong or moderate CYP3A inhibitors within 3 days prior to start of study treatment.
  • Dose Optimization combination cohorts only: Participant has malabsorption syndrome or other condition that precludes enteral route of administration.
  • Dose Optimization combination cohorts only: Participant has promyelocytic leukemia (M3).
  • CRC chemotherapy cohort only: Participant with minor surgical procedures, such as fine needle aspirations or core biopsies, within 7 days prior to first dose of study drug are excluded.
  • Participants in CRC chemotherapy combination cohort only: cardiomyopathy, coronary/peripheral artery bypass graft, aneurysm or aneurysm repair, angioplasty, pulmonary hypertension, cerebrovascular accident or transient ischemic attack, within 1 year of first dose of study drug.
  • Chemotherapy combination CRC participants only: Prior receipt of an irinotecan-based chemotherapy.
  • Chemotherapy combination CRC participants only: Disease progression within 3-months of initiating first-line therapy.
  • Chemotherapy combination CRC participants only: history of Gilbert's syndrome or UG1T1A1 genotypes.
  • Chemotherapy Combination CRC Participants Only: Clinically significant conditions that may place the participant at higher risk with anti-angiogenic therapy.

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
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Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

Locations
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United States, Connecticut
Yale University /ID# 158029 Recruiting
New Haven, Connecticut, United States, 06510
United States, Illinois
University of Chicago /ID# 158030 Completed
Chicago, Illinois, United States, 60637-1443
Ingalls Memorial Hosp /ID# 171221 Recruiting
Harvey, Illinois, United States, 60426
United States, Michigan
Univ Michigan Med Ctr /ID# 207134 Not yet recruiting
Ann Arbor, Michigan, United States, 48109
United States, Rhode Island
Rhode Island Hospital /ID# 171157 Recruiting
Providence, Rhode Island, United States, 02903
United States, Texas
MD Anderson Cancer Center /ID# 202187 Recruiting
Houston, Texas, United States, 77030
South Texas Accelerated Research Therapeutics /ID# 160574 Recruiting
San Antonio, Texas, United States, 78229
United States, Wisconsin
Medical College of Wisconsin /ID# 171152 Recruiting
Milwaukee, Wisconsin, United States, 53226-3522
Japan
National Cancer Ctr Hosp East /ID# 160596 Recruiting
Kashiwa-shi, Chiba, Japan, 277-8577
Yamagata University Hospital /ID# 200681 Recruiting
Yamagata-shi, Yamagata, Japan, 990-9585
Netherlands
Universitair Medisch Centrum Groningen /ID# 169748 Recruiting
Groningen, Netherlands, 9713 GZ
Erasmus Medisch Centrum /ID# 160869 Recruiting
Rotterdam, Netherlands, 3015 CE
Universitair Medisch Centrum Utrecht /ID# 169747 Recruiting
Utrecht, Netherlands, 3584 CX
Spain
Hospital General Vall D'Hebron /ID# 170809 Completed
Barcelona, Spain, 08035
Hospital Fundacion Jimenez Dia /ID# 200106 Recruiting
Madrid, Spain, 28040
Hosp Univ Madrid Sanchinarro /ID# 165136 Recruiting
Madrid, Spain, 28050
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie

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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: August 15, 2019
Last Verified: August 2019
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:
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:
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Neoplasms
Bevacizumab
Venetoclax
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors