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Relapsed Adult AMLPhase 1NCT06007911

Venetoclax-Navitoclax With Cladribine-based Salvage Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia

A Phase 1 study testing Navitoclax Dose Level -1, Navitoclax Dose Level 0 and Navitoclax Dose Level 1 in people with Relapsed Adult AML and Refractory AML, run by Medical College of Wisconsin at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an open-label phase I study designed to evaluate the safety of venetoclax-navitoclax with cladribine-based salvage therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Relapsed Adult AML, Refractory AML
What is being tested?
Navitoclax Dose Level -1, Navitoclax Dose Level 0 and Navitoclax Dose Level 1
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
31 Aug 2024to Apr 2027
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female subjects 18 years or older.
  • Patients must have a diagnosis of morphologically documented AML or secondary AML from prior conditions, such as myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), MDS/MPN, chronic myelomonocytic leukemia (CMML) or therapy-related AML (t-AML), as defined by the World Health Organization (WHO) 2022 criteria.
  • Relapsed or refractory to at least one prior line of therapy.
  • Previous therapy with venetoclax.
  • Eastern Cooperative Oncology Group (ECOG) performance status of:
  • 0-3 for Arm A (i.e., Cladribine-low dose cytarabine backbone arm).
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  • 0-2 for Arm B (i.e., CLAG-M backbone arm).
  • Left ventricular ejection fraction (LVEF) of:
  • LVEF ≥35% for Arm A (i.e., Cladribine-low dose cytarabine backbone arm).
  • LVEF ≥45% for Arm B (i.e., CLAG-M backbone arm).
  • Creatinine clearance (CrCl) as calculated by the Cockroft-Gault formula, of:
  • CrCl ≥ 30 mL/min for Arm A (i.e., Cladribine-low dose cytarabine backbone arm).
  • CrCl ≥ 40 mL/min for Arm B (i.e., CLAG-M backbone arm).
  • Clinical laboratory values within the following parameters:
  • Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) unless attributable to underlying leukemia. Patient with total bilirubin > 1.5 × institutional ULN may enroll if direct bilirubin ≤ 1.5 × institutional ULN of the direct bilirubin.
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × institutional ULN, unless attributable to underlying leukemia.
  • White blood cell (WBC) count < 25,000/µL before Cycle 1, Day 1 of therapy (Note: Hydroxyurea, cytarabine or leukapheresis may be used to meet this criterion.)
  • Platelet count of at least 20,000/µL before Cycle 1, Day 1 of therapy (Note: Platelet transfusion can be used to meet this criterion.)
  • Female subjects who:
  • Are postmenopausal for at least one year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential:
  • Agree to practice one highly effective method and one additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through four months after the last dose of study drug (female and male condoms should not be used together), OR ii. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception).
  • Male subjects, even if surgically sterilized (i.e., status post vasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period from the time of signing the informed consent through and through four months after the last dose of study drug (female and male condoms should not be used together), OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods for the female partner] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
  • Ability to understand a written informed consent document, and the willingness to sign it.

Who cannot join

  • Acute promyelocytic leukemia.
  • Prior therapy with B-cell lymphoma-extra large (BCL-XL) inhibitor.
  • Treatment with systemic antineoplastic therapy within 14 days or five half-lives from the last dose - whichever is longer - before Cycle 1, Day 1 of therapy. Radiation within 14 days before Cycle 1, Day 1 of therapy. The use of hydroxyurea/cytarabine for leukoreduction is permitted.
  • Hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor T-cell therapy (CAR-T cell) within 60 days of enrollment. (If patients had prior allogeneic HCT, they should have no active graft-versus-host disease and should be off calcineurin inhibitors at least four weeks prior to cycle 1 day 1 of therapy.)
  • Current systemic treatment with strong or moderate Cytochrome P4503A (CYP3A) inducers within 7 days prior to Cycle 1, Day 1 of therapy.
  • Presence of another active malignancy requiring systemic treatment within the last 12 months, except for localized cancers that have been adequately treated.
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  • Known HIV positive patients who DO NOT meet the following criteria:
  • Cluster of differentiation (CD) 4 count > 350 cells/mm^3.
  • Undetectable viral load.
  • Maintained on modern therapeutic regimens utilizing non-CYP-interactive agents.
  • No history of AIDS-defining opportunistic infections.
  • Known hepatitis B surface antigen seropositive or active hepatitis C infection. Note: Patients who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
  • Female subjects who are both lactating and breastfeeding or of childbearing potential who have a positive serum test during screening.
  • Female subjects who intend to donate eggs (ova) during the course of the study or four months after receiving their last dose of the study drug(s).
  • Male subjects who intend to donate sperm during the course of this study or four months after receiving their last dose of the study drug(s).
  • Has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit from three days prior to Cycle 1, Day 1 to throughout the study treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Froedtert Hospital & the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

This is an open-label phase I study designed to evaluate the safety of venetoclax-navitoclax with cladribine-based salvage therapy.

Read the detailed description

The primary objective of the study is to determine a maximum-tolerated dose (MTD) combination of venetoclax-navitoclax with cladribine-based salvage therapy. Subjects will be entered sequentially to each dose level. For each dose level, if none of the first three subjects at that level experiences a dose-limiting toxicity (DLT), new subjects may be entered at the next higher dose level. If one of three subjects experience a DLT, up to three more subjects are to be treated at that same dose level. If none of the additional three subjects at that dose level experiences a DLT, new subjects may be entered at the next higher dose level. However, if one or more of the additional three subjects experience a DLT, then no further subjects are to be started at that dose level and either de-escalate one level or if the preceding dose is already completed then that dose is the MTD. The MTD will be defined as the highest dose level at which none of the first three treated subjects, or no more than one of the first six treated subjects, experiences a DLT.

Being tested
Navitoclax Dose Level -1, Navitoclax Dose Level 0, Navitoclax Dose Level 1, Navitoclax Dose Level 2, Venetoclax Dose Level -1
Keywords
Acute Myeloid Leukemia, AML, Venetoclax, Navitoclax, cladribine-based salvage therapy, CLAG-M
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • Navitoclax Dose Level -1Drug

    Also called ABT-263

    25 mg by mouth on days 1-7.

  • Navitoclax Dose Level 0Drug

    Also called ABT-263

    50 mg by mouth on days 1-10.

  • Navitoclax Dose Level 1Drug

    Also called ABT-263

    75 mg by mouth on days 1-10.

  • Navitoclax Dose Level 2Drug

    Also called ABT-263

    100 mg by mouth on days 1-10.

  • Venetoclax Dose Level -1Drug

    Also called Venclexta

    400 mg by mouth on days 1-7.

  • Venetoclax Dose Levels 0 to 2Drug

    Also called Venclexta

    400 mg by mouth on days 1-14.

  • CladribineDrug

    Also called Mavenclad, Leustatin DSC

    5 mg/m^2 intravenously days 1-5.

  • Cytarabine (Cladribine Low Dose Cytarabine Backbone)Drug

    Also called ara-C

    20 mg/m^2 subcutaneous days 1-10.

  • Cytarabine (CLAG-M Backbone)Drug

    Also called ara-C

    1.5 g/m^2 intravenously days 1-5.

  • MitoxantroneDrug

    Also called Novantrone

    10 mg/m^2 intravenously days 1-3.

  • Granulocyte Colony-Stimulating FactorDrug

    Also called G-CSF, filgrastim, Neupogen

    300 mcg subcutaneously days 1-5.

Study groups in NCT06007911
Study groupRoleWhat they receive
Cladribine-Low Dose Cytarabine Backbone Dose Level -1ExperimentalDose level -1 will be considered only if there are dose-limiting toxicities at dose level 0. This is a regimen of navitoclax, venetoclax, cladribine and cytarabine.
Receives: Drug: Navitoclax Dose Level -1; Drug: Venetoclax Dose Level -1; Drug: Cladribine; Drug: Cytarabine (Cladribine Low Dose Cytarabine Backbone)
Cladribine-Low Dose Cytarabine Backbone Dose Level 0ExperimentalThis is a regimen of navitoclax, venetoclax, cladribine and cytarabine.
Receives: Drug: Navitoclax Dose Level 0; Drug: Venetoclax Dose Levels 0 to 2; Drug: Cladribine; Drug: Cytarabine (Cladribine Low Dose Cytarabine Backbone)
Cladribine-Low Dose Cytarabine Backbone Dose Level 1ExperimentalThis is a regimen of navitoclax, venetoclax, cladribine and cytarabine.
Receives: Drug: Navitoclax Dose Level 1; Drug: Venetoclax Dose Levels 0 to 2; Drug: Cladribine; Drug: Cytarabine (Cladribine Low Dose Cytarabine Backbone)
Cladribine-Low Dose Cytarabine Backbone Dose Level 2ExperimentalThis is a regimen of navitoclax, venetoclax, cladribine and cytarabine.
Receives: Drug: Navitoclax Dose Level 2; Drug: Venetoclax Dose Levels 0 to 2; Drug: Cladribine; Drug: Cytarabine (Cladribine Low Dose Cytarabine Backbone)
Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)ExperimentalThe MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a dose-limiting toxicity.
Receives: Drug: Navitoclax Dose Level -1; Drug: Navitoclax Dose Level 0; Drug: Navitoclax Dose Level 1; Drug: Navitoclax Dose Level 2; Drug: Venetoclax Dose Level -1; Drug: Venetoclax Dose Levels 0 to 2; Drug: Cladribine; Drug: Cytarabine (Cladribine Low Dose Cytarabine Backbone)
CLAG-M Backbone Level -1ExperimentalDose level -1 will be considered only if there are dose-limiting toxicities at dose level 0. This is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and G-CSF.
Receives: Drug: Navitoclax Dose Level -1; Drug: Venetoclax Dose Level -1; Drug: Cladribine; Drug: Cytarabine (CLAG-M Backbone); Drug: Mitoxantrone; Drug: Granulocyte Colony-Stimulating Factor
CLAG-M Backbone Level 0ExperimentalThis is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and granulocyte colony-stimulating factor (G-CSF).
Receives: Drug: Navitoclax Dose Level 0; Drug: Venetoclax Dose Levels 0 to 2; Drug: Cladribine; Drug: Cytarabine (CLAG-M Backbone); Drug: Mitoxantrone; Drug: Granulocyte Colony-Stimulating Factor
CLAG-M Backbone Level 1ExperimentalThis is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and G-CSF.
Receives: Drug: Navitoclax Dose Level 1; Drug: Venetoclax Dose Levels 0 to 2; Drug: Cladribine; Drug: Cytarabine (CLAG-M Backbone); Drug: Mitoxantrone; Drug: Granulocyte Colony-Stimulating Factor
CLAG-M Backbone Level 2ExperimentalThis is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and G-CSF.
Receives: Drug: Navitoclax Dose Level 2; Drug: Venetoclax Dose Levels 0 to 2; Drug: Cladribine; Drug: Cytarabine (CLAG-M Backbone); Drug: Mitoxantrone; Drug: Granulocyte Colony-Stimulating Factor
CLAG-M Backbone Maximum Tolerated DoseExperimentalThe MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a dose-limiting toxicity.
Receives: Drug: Navitoclax Dose Level -1; Drug: Navitoclax Dose Level 0; Drug: Navitoclax Dose Level 1; Drug: Navitoclax Dose Level 2; Drug: Venetoclax Dose Level -1; Drug: Venetoclax Dose Levels 0 to 2; Drug: Cladribine; Drug: Cytarabine (CLAG-M Backbone); Drug: Mitoxantrone; Drug: Granulocyte Colony-Stimulating Factor

What is being measured

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

  1. Recommended Phase 2 Dose of Navitoclax for the Cladribine-Low Dose Cytarabine Backbone

    The dose identified in this trial that will be used in future clinical trials.

    Measured: Up to three years

  2. Recommended Phase 2 Dose for Navitoclax for the CLAG-M Backbone

    The dose identified in this trial that will be used in future clinical trials.

    Measured: Up to three years

Timeline

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

  1. First posted23 Aug 2023
  2. Study start31 Aug 2024 (estimated)
  3. Primary completionDec 2025 (estimated)
  4. Study completionApr 2027 (estimated)

Why it stopped: Sponsor withdrew support.

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06007911
Sponsor's protocol ID
PRO00050186
Status last verified
Aug 2024
First submitted
17 Aug 2023
Last updated
13 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Navitoclax Dose Level -1, Navitoclax Dose Level 0 and Navitoclax Dose Level 1 in people with Relapsed Adult AML and Refractory AML, run by Medical College of Wisconsin at 1 site in United States.

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 27 inclusion and 16 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: withdrawn, as of the sponsor's last update on 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 was withdrawn before enrolling participants, so there are no results.

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?

Recommended Phase 2 Dose of Navitoclax for the Cladribine-Low Dose Cytarabine Backbone (time frame: Up to three years). The study lists 2 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 NCT06007911.

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 13 Aug 2024.

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