NCT04797767

Brief Summary

This phase I/II trial finds the best dose, side effects and how well giving venetoclax in combination with cladribine, cytarabine, granulocyte colony-stimulating factor, and mitoxantrone (CLAG-M) in treating patients with acute myeloid leukemia and high-grade myeloid neoplasms. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as cladribine, cytarabine, and mitoxantrone, 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. Giving venetoclax with CLAG-M may kill more cancer cells.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
62

participants targeted

Target at P75+ for phase_1

Timeline
32mo left

Started Feb 2022

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress62%
Feb 2022Dec 2028

First Submitted

Initial submission to the registry

March 10, 2021

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 15, 2021

Completed
11 months until next milestone

Study Start

First participant enrolled

February 4, 2022

Completed
5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2027

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

April 17, 2026

Status Verified

April 1, 2026

Enrollment Period

5.9 years

First QC Date

March 10, 2021

Last Update Submit

April 14, 2026

Conditions

Acute Biphenotypic LeukemiaAcute Myeloid LeukemiaMixed Phenotype Acute LeukemiaMyeloid NeoplasmRelapsed Acute Biphenotypic LeukemiaRelapsed Acute Myeloid LeukemiaRelapsed Mixed Phenotype Acute LeukemiaRelapsed Myeloid NeoplasmRefractory Acute Biphenotypic LeukemiaRefractory Acute Myeloid LeukemiaRefractory Mixed Phenotype Acute LeukemiaRefractory Myeloid NeoplasmRecurrent Myeloid Sarcoma

Outcome Measures

Primary Outcomes (3)

  • Incidence of adverse events (Phase I)

    Up to 12 months

  • Maximum tolerated dose of venetoclax in combination with CLAG-M (Phase I)

    Up to 12 months

  • Event free survival (Phase II)

    At 6 months

Secondary Outcomes (4)

  • Complete remission rate

    After 2 cycles (each cycle is approximately 35 days)

  • Rate of minimal residual disease negativity

    Up to 1 year

  • Rate of allogeneic hematopoietic cell transplant

    At 1 year

  • Overall survival

    At 1 year

Study Arms (1)

Treatment (CLAG-M, venetoclax)

EXPERIMENTAL

Patients will receive induction with granulocyte colony-stimulating factor on days 0-5 (if peripheral white blood cell count is less than 20,000/uL), cladribine on days 1-5, cytarabine on 1-5, and mitoxantrone on days 1-3. Patients also receive venetoclax orally (PO) on days 1-14. Treatment repeats every 28-35 days for up to 2 induction cycles including mitoxantrone, and up to 4 consolidation cycles without mitoxantrone in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy and/or aspiration, and blood sample collection throughout the study.

Drug: CladribineDrug: CytarabineDrug: MitoxantroneBiological: Recombinant Granulocyte Colony-Stimulating FactorDrug: VenetoclaxProcedure: Bone Marrow AspirationProcedure: Bone Marrow BiopsyProcedure: Biospecimen Collection

Interventions

CladribineDRUG

Given IV

Also known as: 2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251
Treatment (CLAG-M, venetoclax)
CytarabineDRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453
Treatment (CLAG-M, venetoclax)
MitoxantroneDRUG

Given IV

Also known as: Dihydroxyanthracenedione, Mitozantrone
Treatment (CLAG-M, venetoclax)
Recombinant Granulocyte Colony-Stimulating FactorBIOLOGICAL

Given subcutaneously

Also known as: Recombinant Colony-Stimulating Factor 3, rhG-CSF
Treatment (CLAG-M, venetoclax)
VenetoclaxDRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto
Treatment (CLAG-M, venetoclax)
Bone Marrow AspirationPROCEDURE

Undergo bone marrow aspiration

Treatment (CLAG-M, venetoclax)
Bone Marrow BiopsyPROCEDURE

Undergo bone marrow biopsy

Treatment (CLAG-M, venetoclax)
Biospecimen CollectionPROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection
Treatment (CLAG-M, venetoclax)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of acute myeloid leukemia (per the World Health Organization \[WHO\] 2016 classification) or high-grade myeloid neoplasm (\>= 10% myeloid blasts in peripheral blood or marrow as assessed by morphology or multiparameter flow cytometry at initial presentation). Patients with biphenotypic or mixed phenotype acute leukemia are eligible.
  • PHASE I:
  • Newly diagnosed patients presenting for trial entry must have adverse risk disease as per the European LeukemiaNet 2017 guidelines
  • Relapsed/refractory patients presenting for trial entry must require first or subsequent salvage therapy and have detectable blasts in peripheral blood or \>= 5% blasts in bone marrow, as assessed by morphology or multiparameter flow cytometry; or extramedullary myeloid sarcoma, per European LeukemiaNet 2017 guidelines.
  • These patients are only allowed in the phase 1 portion of the trial
  • PHASE II: Newly diagnosed patients presenting for trial entry must have adverse risk disease as per the European LeukemiaNet 2022 guidelines
  • Age \>= 18 years
  • Aspartate transaminase (AST) and alanine transaminase (ALT) =\< 3.0 X upper limit of normal (ULN)
  • Bilirubin =\< 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
  • Subject must have adequate renal function as demonstrated by a creatinine clearance \>= 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection
  • Left ventricular ejection fraction (LVEF) \>= 45%, assessed by multigated acquisition (MUGA) or echocardiogram (ECHO) within 3 months prior to study day 0 or after most recent anthracycline administration if appropriate and no clinical evidence of congestive heart failure
  • Eastern Cooperative Oncology Group (ECOG) =\< 2
  • Treatment-related mortality (TRM) score \< 13.1
  • Female subjects of childbearing potential must have negative results for pregnancy test. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use an effective method of birth control from the time of signing the consent form until at least 3 months after the last dose of study drug
  • Ability to understand and the willingness to sign a written informed consent document
  • +1 more criteria

You may not qualify if:

  • Acute promyelocytic leukemia or chronic myeloid leukemia in myeloid blast crisis
  • Known active central nervous system (CNS) involvement with acute myeloid leukemia (AML)
  • Concomitant illness associated with a likely survival of \< 1 year
  • Active systemic infection, unless disease is under treatment with antimicrobials and considered controlled or stable; patients with fever thought to be likely secondary to leukemia are eligible. Patients with chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment would be excluded. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface \[HBs\] antigen negative-, anti-HBs antibody positive and anti-hepatitis B core \[HBc\] antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate
  • Known hypersensitivity to any study drug
  • Pregnancy or lactation because of the unknown risks of this combination
  • Concurrent treatment with any other investigational agent
  • Subject is known to be positive for human immunodeficiency virus (HIV)
  • Subjects who cannot discontinue concomitant CYP3A inhibitors, except for voriconazole, prior to cycle 1 day 1 (C1D1)
  • Treatment with any of the following within 7 days prior to the first dose of venetoclax
  • Steroid therapy for anti-neoplastic intent
  • Administration or consumption of any of the following within 3 days prior to the first dose of venetoclax:
  • Grapefruit or grapefruit products
  • Seville oranges (including marmalade containing Seville oranges)
  • Star fruit

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (1)

  • Raychaudhuri S, Gooley TA, Rasmussen A, Quach K, Gill E, Halpern AB, Appelbaum JS, Ghiuzeli CM, Hendrie PC, Cassaday RD, Walter RB, Percival MM. Phase 1 trial of venetoclax with cladribine, cytarabine, G-CSF, and mitoxantrone for AML and high-grade myeloid neoplasm. Blood Neoplasia. 2025 Mar 3;2(3):100085. doi: 10.1016/j.bneo.2025.100085. eCollection 2025 Aug.

    PMID: 40535475DERIVED

MeSH Terms

Conditions

Leukemia, Biphenotypic, AcuteLeukemia, Myeloid, AcuteSarcoma, Myeloid

Interventions

CladribineCytarabineMitoxantronepegylated granulocyte colony-stimulating factorvenetoclax

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, MyeloidSarcomaNeoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

2-ChloroadenosineAdenosinePurine NucleosidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDeoxyadenosinesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingArabinonucleosidesAnthraquinonesAnthronesAnthracenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsQuinonesPolycyclic Compounds

Study Officials

  • Mary-Beth M. Percival

    Fred Hutch/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Kim Quach

CONTACT

206.606.8311kquach@fredhutch.org

Mary-Beth M. Percival

CONTACT

206.606.1320mperciva@fredhutch.org

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 10, 2021

First Posted

March 15, 2021

Study Start

February 4, 2022

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2028

Last Updated

April 17, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

US(1)