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Recurrent Acute Myeloid LeukemiaPhase 1NCT05222984

Navitoclax, Venetoclax, and Decitabine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Previously Treated With Venetoclax

A Phase 1 study testing Decitabine, Navitoclax and Venetoclax in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase Ib trial is to find the side effect and best dose of navitoclax when given together with venetoclax and decitabine in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory) after previous treatment with venetoclax. Read more about this study

Who is it for?
Ages 16 years and older
What is being tested?
Decitabine, Navitoclax and Venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
16 Sep 2022to 2 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

Who may be able to join

  • Documented informed consent of the participant and/or legally authorized representative
  • For participants under the age of 18 years, documentation of adolescent assent by the participant and consent of both parents or guardian
  • Adults aged >= 18 years
  • Adolescent patients aged >= 16 years and < 18 years weighing at least 45 kg who have no other standard-of-care option for treatment
  • Eastern Cooperative Oncology Group (ECOG) =< 2
  • Patients with histologically confirmed AML, according to World Health Organization (WHO) criteria, with refractory/relapsed (R/R) disease following a venetoclax-containing regimen who are ineligible for therapies known to be effective for treatment of their AML.
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  • Patients with extramedullary disease may be included if they also have marrow involvement
  • Patients with acute promyelocytic leukemia (APL) will not be eligible
  • Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 of prior anti-cancer therapy
  • Ability to swallow pills
  • Absolute neutrophil count (ANC) >= 750/mm^3 (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
  • White blood cell (WBC) =< 25 x 10^9/L prior to initiation of study therapy. Cytoreduction with hydroxyurea prior to treatment and/or during cycle 1 may be required (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • Platelets >= 75,000/mm^3
  • NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
  • Total bilirubin =< 1.5 X upper limit of normal (ULN) (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • Aspartate aminotransferase (AST) =< 3.0 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • Alanine aminotransferase (ALT) =< 3.0 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • Creatinine clearance of >= 45 ml/min per 24-hour urine test or the Cockcroft-Gault formula (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • If in the absence of anticoagulants: International normalized ratio (INR) OR prothrombin (PT) =< 1.5 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • If in the absence of anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • Left ventricular ejection fraction (LVEF) >= 50%
  • Note: To be performed within 28 days prior to day 1 of protocol therapy
  • Corrected QT interval (QTc) =< 480 ms
  • Note: To be performed within 28 days prior to day 1 of protocol therapy
  • Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (RPR) (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • If positive, Hepatitis C RNA quantitation must be performed
  • Meets other institutional and federal requirements for infectious disease titer requirements
  • Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
  • Women of child-bearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months (males) and 6 months (females) after the last dose of protocol therapy
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Who cannot join

  • Hematopoietic stem cell transplant within 100 days prior to day 1 of protocol therapy
  • Chemotherapy, radiation therapy, biological therapy, or immunotherapy within 14 days or 5 half-lives, whichever is shorter, prior to day 1 of protocol therapy with the following exceptions:
  • Subjects will be allowed to have been on venetoclax at screening and remain on it through treatment start.
  • Hydroxyurea is allowed prior to treatment and through cycle 1 for control of rapidly progressing leukemia
  • Strong or moderate CYP3A4 inducers within 14 days prior to day 1 of protocol therapy
  • Grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit consumed within 3 days prior to the first dose of study drug
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  • Immunosuppressants (steroids =< 10 mg/day of oral prednisone or equivalent is allowed) within the last 28 days
  • Hematopoietic growth factors in the last 14 days
  • Must not have received or planning to receive live vaccine while being on study or 4 weeks before and after completion of treatment
  • Herbal medications known to affect platelet function within 14 days of therapy initiation
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  • Active graft-versus-host-disease (GVHD)
  • Active central nervous system (CNS) disease
  • No measurable disease in the bone marrow
  • Active diarrhea
  • Gastrointestinal disorder that interferes with oral drug absorption such as malabsorption syndrome
  • Clinically significant cardiac morbidities (class III/IV cardiovascular disability according to the New York Heart Association classification, arrhythmia not stable on medical management, acute cardiovascular ischemic event within 6 months of enrollment, etc.)
  • Clinically significant uncontrolled illness
  • Active infection requiring antibiotics
  • Active/uncontrolled HIV infection, acquired immunodeficiency syndrome (AIDS), or currently taking contraindicated medications for HIV control
  • Diagnosis of Gilbert's disease
  • Any other active malignancy at time of enrollment. Exceptions include basal/squamous cell carcinoma, in situ adequately treated breast and uterine cancer
  • Females only: Pregnant or breastfeeding
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase Ib Open Label Study of Navitoclax in Combination With Venetoclax + Decitabine in Relapsed/Refractory Acute Myeloid Leukemia Previously Treated With Venetoclax

This phase Ib trial is to find the side effect and best dose of navitoclax when given together with venetoclax and decitabine in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory) after previous treatment with venetoclax. Chemotherapy drugs, such as navitoclax, venetoclax, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Assess safety and determine the optimal biological doses (OBD). II. Evaluate the anti-leukemic activity, as assessed by overall response rate (ORR: complete response [CR] + complete response with incomplete hematopoiesis [CRi] + partial response [PR]) within the first 35 days (cycle 1).

SECONDARY OBJECTIVES:

  1. Characterize safety and tolerability of navitoclax/venetoclax during the first 7 days of cycle 1.

II. Obtain preliminary estimates of:

IIa. Overall response (CR+CRi+PR) duration. IIb. Progression free survival (PFS) and overall survival (OS) rates at 6-months and 1-year.

CORRELATIVE STUDY OBJECTIVES:

  1. Describe the anti-leukemic activity (i.e. decrease in percent blasts) of navitoclax/venetoclax as assessed by disease in bone marrow (BM) and/or peripheral blood (PB).

II. Explore the potential relationship between changes in BH3 protein expression profiles (pre- and post-treatment) and response.

III. Profile the clonal evolution of acute myeloid leukemia (AML) in response to treatment by single cell next generation sequencing (NGS) of whole exomes and the ribonucleic acid (RNA) transcriptome.

IV. Profile the clonal evolution of AML in response to treatment by single cell NGS of the mitochondrial genome.

  1. Determine mitochondrial number and heteroplasmy and changes in response to treatment.

VI. Determine the impact of treatment on leukemic stem cell (LSC) burden by examining bone marrow (BM)-derived mononuclear cells (MNC) for their ability to initiate leukemia in in vivo mouse models pre- and post-treatment.

OUTLINE: This is a dose-escalation study of navitoclax.

Patients receive venetoclax orally (PO) once daily (QD) and navitoclax PO QD on days 1-35, and decitabine intravenously (IV) over 1 hour on days 8-12 of cycle 1. Starting on cycle 2, patients receive venetoclax PO QD and navitoclax PO QD on days 1-28, and decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year.

Being tested
Decitabine, Navitoclax, Venetoclax
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.

  • DecitabineDrug

    Also called 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine

    Given IV

  • NavitoclaxBiological

    Also called A-855071.0, ABT-263, BcI-2 Family Protein Inhibitor ABT-263

    Given PO

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

Study groups in NCT05222984
Study groupRoleWhat they receive
Treatment (navitoclax, venetoclax, decitabine)ExperimentalPatients receive venetoclax PO QD and navitoclax PO QD on days 1-35, and decitabine IV over 1 hour on days 8-12 of cycle 1. Starting on cycle 2, patients receive venetoclax PO QD and navitoclax PO QD on days 1-28, and decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Decitabine; Biological: Navitoclax; Drug: Venetoclax

What is being measured

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

  1. Incidence of adverse events

    Will be assessed and graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 1 year

Secondary outcomes (4)

  1. Overall response rate

    Will be calculated as the percent of evaluable patients that have confirmed complete response (CR) or complete response with incomplete hematopoiesis or partial response. Assessment of disease response will be made according to European LeukemiaNet criteria.

    Measured: Up to 1 year

  2. Progression Free Survival (PFS)

    From the start of study treatment to the time of disease relapse, progression or death from any cause, whichever comes first. assessed up to 1 year

    Measured: Assessed up to 1 year

  3. Overall Survival (OS)

    Time from the start of study treatment to death from any cause.

    Measured: Assessed up to 1 year

  4. Dose Limiting Toxicity (DLT)

    DLT will be evaluated in the first 35 days of treatment in the safety cohort to determine any dose limiting toxicities at this dose.

    Measured: Up to 35 days (1 cycle)

Timeline

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

  1. First posted3 Feb 2022
  2. Study start16 Sep 2022
  3. Primary completion2 Mar 2027 (estimated)
  4. Study completion2 Mar 2027 (estimated)

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
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05222984
Sponsor's protocol ID
22178
Other IDs
NCI-2021-05552, 20398, P30CA033572
Status last verified
Oct 2026
First submitted
10 Jan 2022
Last updated
14 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Decitabine, Navitoclax and Venetoclax in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by City of Hope Medical Center 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 32 inclusion and 25 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: under way, not looking for participants, as of the sponsor's last update on 14 Oct 2026. 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?

This study is still under way. Results are not available in the source record yet.

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?

Incidence of adverse events (time frame: Up to 1 year). 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 NCT05222984.

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 2026.

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