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Acute Lymphoblastic Leukemia (ALL)Phase 1NCT03181126

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

A Phase 1 study testing Navitoclax, Chemotherapy and Venetoclax in people with Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma, run by AbbVie at 15 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 4 years and older
What is being tested?
Navitoclax, Chemotherapy and Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
15 sitesin 2 countries
Study dates
27 Nov 2017to 14 Nov 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States12 sites

  • Univ NC Chapel Hill /ID# 163509

    Chapel Hill, North Carolina, 27514-4220

  • University of Chicago /ID# 163369

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital /ID# 164619

    Cincinnati, Ohio, 45229

  • Nationwide Childrens Hospital /ID# 163372

    Columbus, Ohio, 43205

  • UT Southwestern Medical Center /ID# 163346

    Dallas, Texas, 75390-7208

  • City of Hope /ID# 169029

    Duarte, California, 91010

  • MD Anderson Cancer Center at Texas Medical Center /ID# 163327

    Houston, Texas, 77030-4000

  • University of Wisconsin-Madiso /ID# 165691

    Madison, Wisconsin, 53705

  • St Jude Children's Research Hospital /ID# 163335

    Memphis, Tennessee, 38105

  • LPCH Stanford /ID# 163337

    Palo Alto, California, 94304

  • Oregon Health and Science University /ID# 165690

    Portland, Oregon, 97239

  • Washington University-School of Medicine /ID# 165689

    St Louis, Missouri, 63110

Other trials in United States

Australia3 sites

  • Alfred Hospital /ID# 169576

    Melbourne, Victoria, 3004

  • Victorian Comprehensive Cancer /ID# 165710

    Melbourne, Victoria, 3050

  • Royal Children's Hospital /ID# 163322

    Melbourne, Victoria, 3052

Other trials in Australia

About this study

Official title: 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.

Being tested
Navitoclax, Chemotherapy, Venetoclax
Keywords
Relapsed of Refractory Acute Lymphoblastic Leukemia, Cancer, Venetoclax, Navitoclax
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NavitoclaxDrug

    Also called ABT-263

    tablet

  • ChemotherapyDrug

    peg-asparaginase (or other form of asparaginase, per local standard of care (intravenous) + vincristine (intravenous) + dexamethasone (oral) + tyrosine kinase inhibitor (TKI) (if applicable, oral)

  • VenetoclaxDrug

    Also called ABT-199 GDC-0199

    tablet

Study groups in NCT03181126
Study groupRoleWhat they receive
Venetoclax + Navitoclax + ChemotherapyExperimentalVenetoclax 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.
Receives: Drug: Navitoclax; Drug: Chemotherapy; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cmax of Venetoclax + Navitoclax

    Maximum observed plasma concentration (Cmax) of venetoclax + navitoclax

    Measured: Up to approximately 9 months

  2. AUC of Venetoclax + Navitoclax

    Area under the plasma concentration-time curve (AUC) of venetoclax + navitoclax

    Measured: Up to approximately 9 months

  3. Tmax of Venetoclax + Navitoclax

    Time to Cmax (Tmax) of Venetoclax + Navitoclax

    Measured: Up to approximately 9 months

  4. CL/F of Venetoclax + Navitoclax

    Apparent oral clearance (CL/F) of venetoclax + navitoclax

    Measured: Up to approximately 9 months

  5. Number of participants with dose-limiting toxicities (DLT)

    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.

    Measured: Up to approximately 28 days after initial dose of study drug

Secondary outcomes (6)

  1. Progression-free survival (PFS)

    PFS is defined as the number of days from the date of enrollment to the date of earliest disease progression or death.

    Measured: Up to 9 months after the last subject has enrolled into the study

  2. Partial Response (PR) rate

    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.

    Measured: Up to 9 months after the last subject has enrolled into the study

  3. Number of Participant who Proceed to Stem Cell Transplantation or Chimeric antigen receptor T-cell (CAR-T) Therapy

    Determine the number of participants who proceed to stem cell transplantation or CAR-T therapy.

    Measured: Up to 9 months after the last subject has enrolled into the study

  4. Overall survival (OS)

    OS is defined as the number of days from the date of enrollment to the date of death.

    Measured: Up to 9 months after the last subject has enrolled into the study

  5. Objective response rate (ORR)

    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.

    Measured: Up to 9 months after the last subject has enrolled into the study

  6. Complete Response (CR) rate

    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.

    Measured: Up to 9 months after the last subject has enrolled into the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jun 2017
  2. Study start27 Nov 2017
  3. Primary completion11 Nov 2020
  4. Study completion14 Nov 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03181126
Sponsor's protocol ID
M16-106
Status last verified
Oct 2021
First submitted
5 Jun 2017
Last updated
14 Oct 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided
Expanded access
Available

Publications

  • Badawi M, Gopalakrishnan S, Engelhardt B, Palenski T, Karol SE, Rubnitz JE, Menon R, Salem AH. Dosing of Venetoclax in Pediatric Patients with Relapsed Acute Myeloid Leukemia: Analysis of Developmental Pharmacokinetics and Exposure-Response Relationships. Clin Ther. 2024 Oct;46(10):759-767. doi: 10.1016/j.clinthera.2024.09.008. Epub 2024 Oct 5.

    PubMed 39368878

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Navitoclax, Chemotherapy and Venetoclax in people with Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma, run by AbbVie at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cmax of Venetoclax + Navitoclax (time frame: Up to approximately 9 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03181126, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2021.

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