A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma

October 7, 2021 updated by: AbbVie

A Phase 1 Dose Escalation, Open-Label Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma

This dose-escalating study is to determine the safety, pharmacokinetics, and preliminary efficacy of venetoclax in combination with navitoclax and chemotherapy in adult and pediatric participants with relapsed/refractory acute lymphoblastic leukemia (ALL) or relapsed/refractory lymphoblastic lymphoma. A safety expansion cohort of approximately 20 patients may be enrolled in addition to the 50 participants in dose-escalation cohort.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
69

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
Available

Available

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Alfred Hospital /ID# 169576
      • Melbourne, Victoria, Australia, 3050
        • Victorian Comprehensive Cancer /ID# 165710
      • Melbourne, Victoria, Australia, 3052
        • Royal Children's Hospital /ID# 163322
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope /ID# 169029
      • Palo Alto, California, United States, 94304
        • LPCH Stanford /ID# 163337
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago /ID# 163369
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University-School of Medicine /ID# 165689
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514-4220
        • Univ NC Chapel Hill /ID# 163509
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital /ID# 164619
      • Columbus, Ohio, United States, 43205
        • Nationwide Childrens Hospital /ID# 163372
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University /ID# 165690
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St Jude Children's Research Hospital /ID# 163335
    • Texas
      • Dallas, Texas, United States, 75390-7208
        • UT Southwestern Medical Center /ID# 163346
      • Houston, Texas, United States, 77030-4000
        • MD Anderson Cancer Center at Texas Medical Center /ID# 163327
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • University of Wisconsin-Madiso /ID# 165691

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

4 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must have relapsed or refractory acute lymphoblastic leukemia (ALL) or relapsed or refractory lymphoblastic lymphoma (LL). Refractory is defined as persistent disease after at least 2 courses of chemotherapy.

    • Participants with ALL with Philadelphia chromosome or with an ABL class targetable fusion are eligible.
    • Participants with LL must have radiographic evidence of disease
  • Participants <= 18 years of age who do not have a standard of care treatment option available.
  • Must weigh greater than or equal to 20 kg.
  • Must be able to swallow pills.
  • Must have adequate hepatic and kidney function.

  • Must have adequate performance status:

    • Participants less than or equal to 16 years of age: Lansky greater than or equal to 50
    • Participants greater than 16 years of age: Karnofsky greater than or equal to 50 or Eastern Cooperative Oncology Group (ECOG) less than 3.

Exclusion Criteria:

  • Participant has central nervous system (CNS) disease with cranial involvement that requires radiation.
  • Participants who are less than 100 days post-transplant, or greater than 100 days post-transplant with active graft versus host disease (GVHD), or are still continuing post-transplant immunosuppressant therapy within 7 days prior to the first dose of study drug.

  • Participants who have received any of the following prior to the first dose of study drug:

    • Inotuzumab within 30 days (if participant received inotuzumab > 30 days prior to Day 1, must have ALT, AST and bilirubin < ULN).
    • A biologic agent (i.e., monoclonal antibodies) for anti-neoplastic intent within 30 days
    • CAR-T infusion or other cellular therapy within 30 days

    • Any anti-cancer therapy including blinatumomab, chemotherapy, radiation therapy targeted small molecule agents or investigational agents within 14 days, or 5 half-lives, whichever is shorter

      • Exception: Philadelphia Chromosome (Ph)+ ALL subjects on TKIs at Screening may enroll and remain on Tyrosine Kinase Inhibitor (TKI) therapy to control disease. Participants on venetoclax at screening may enroll and remain on venetoclax.
    • Steroid therapy for anti-neoplastic intent within 5 days
    • Hydroxyurea that is ongoing (hydroxyurea is permitted up to the first dose)
    • A strong or moderate CYP3A inhibitor or inducer within 7 days
    • Aspirin within 7 days, or 5 half-lives, whichever is longer
    • An excluded antiplatelet/anticoagulant drug or a herbal supplement that affects platelet function within 7 days, or 5 half-lives, whichever is longer
  • Participants with malabsorption syndrome or any other condition that precludes enteral administration.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Venetoclax + Navitoclax + Chemotherapy
Venetoclax weight-adjusted doses administered orally every day (QD) starting on Day 1 + navitoclax various, weight-adjusted doses administered orally QD starting on Day 3 + chemotherapy (peg-asparaginase [or any other forms of asparaginase], vincristine, dexamethasone) and tyrosine kinase inhibitor [TKI, if applicable]). This regimen and any of its components may be delayed, reduced or omitted at the discretion of the Investigator.
Drug: Navitoclax
tablet
Other Names:
  • ABT-263
Drug: Chemotherapy
peg-asparaginase (or other form of asparaginase, per local standard of care (intravenous) + vincristine (intravenous) + dexamethasone (oral) + tyrosine kinase inhibitor (TKI) (if applicable, oral)
Drug: Venetoclax
tablet
Other Names:
  • ABT-199 GDC-0199

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cmax of Venetoclax + Navitoclax
Time Frame: Up to approximately 9 months
Maximum observed plasma concentration (Cmax) of venetoclax + navitoclax
Up to approximately 9 months
AUC of Venetoclax + Navitoclax
Time Frame: Up to approximately 9 months
Area under the plasma concentration-time curve (AUC) of venetoclax + navitoclax
Up to approximately 9 months
Tmax of Venetoclax + Navitoclax
Time Frame: Up to approximately 9 months
Time to Cmax (Tmax) of Venetoclax + Navitoclax
Up to approximately 9 months
CL/F of Venetoclax + Navitoclax
Time Frame: Up to approximately 9 months
Apparent oral clearance (CL/F) of venetoclax + navitoclax
Up to approximately 9 months
Number of participants with dose-limiting toxicities (DLT)
Time Frame: Up to approximately 28 days after initial dose of study drug
A DLT is any Grade 3 or higher non-hematologic adverse event (AE) with exceptions outlined in the protocol. AEs and toxicities that occur beyond the DLT assessment period will also be evaluated by the investigator and AbbVie and may be considered as dose-limiting.
Up to approximately 28 days after initial dose of study drug

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: Up to 9 months after the last subject has enrolled into the study
PFS is defined as the number of days from the date of enrollment to the date of earliest disease progression or death.
Up to 9 months after the last subject has enrolled into the study
Partial Response (PR) rate
Time Frame: Up to 9 months after the last subject has enrolled into the study
PR defined as no peripheral blasts or peripheral blood absolute blast count decreased by ≥ 50% from baseline, bone marrow with 5 - 25% blasts and at least a 50% decrease in bone marrow blast percent from baseline, no evidence of extramedullary disease.
Up to 9 months after the last subject has enrolled into the study
Number of Participant who Proceed to Stem Cell Transplantation or Chimeric antigen receptor T-cell (CAR-T) Therapy
Time Frame: Up to 9 months after the last subject has enrolled into the study
Determine the number of participants who proceed to stem cell transplantation or CAR-T therapy.
Up to 9 months after the last subject has enrolled into the study
Overall survival (OS)
Time Frame: Up to 9 months after the last subject has enrolled into the study
OS is defined as the number of days from the date of enrollment to the date of death.
Up to 9 months after the last subject has enrolled into the study
Objective response rate (ORR)
Time Frame: Up to 9 months after the last subject has enrolled into the study
The proportion of subjects with objective response rate (complete response [CR] + CR incomplete recovery [CRi] + CR without platelet recovery [CRp]) for ALL subjects and (CR+PR) for LL subjects.
Up to 9 months after the last subject has enrolled into the study
Complete Response (CR) rate
Time Frame: Up to 9 months after the last subject has enrolled into the study
CR defined as hematologic recovery (absolute neutrophil count [ANC] greater than or equal to 500/μL; platelet counts greater than or equal to 75,000/μL), evidence of trilineage hematopoiesis in the bone marrow and less than 5% blasts in the bone marrow, absence of circulating blasts, and no evidence of extramedullary disease.
Up to 9 months after the last subject has enrolled into the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 27, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 11, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 14, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 5, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 8, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 14, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • M16-106

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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