Acute Biphenotypic LeukemiaPhase 1/2NCT04797767
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
A Phase 1/2 study testing Cladribine, Cytarabine and Mitoxantrone in people with Acute Biphenotypic Leukemia and Acute Myeloid Leukemia, run by University of Washington at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Biphenotypic Leukemia, Acute Myeloid Leukemia, Mixed Phenotype Acute Leukemia
- What is being tested?
- Cladribine, Cytarabine and Mitoxantrone
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Feb 2022to 31 Dec 2028
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 18Show fewer
- Newly diagnosed patients presenting for trial entry must have adverse risk disease as per the European LeukemiaNet 2022 guidelines
- Prior treatment for low-grade myeloid neoplasms (< 10% myeloid blasts in peripheral blood or marrow) is allowed (e.g. Azacitidine/decitabine, lenalidomide, growth factors). Prior treatment treated for antecedent high-grade myeloid neoplasms (≥ 10% myeloid blasts in peripheral blood or marrow) is not allowed
- 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
- White blood cell count in peripheral blood must be < 25,000/ul prior to initiation of study therapy (CLAG-M plus venetoclax). Cytoreduction with hydroxyurea and/or cytarabine (e.g., 500 mg/m^2 per dose) is allowed to decrease the risk of tumor lysis syndrome
Who cannot join
- Acute promyelocytic leukemia or chronic myeloid leukemia in 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
Kim Quach, 206-606-8311, kquach@fredhutch.org
Mary-Beth M. Percival, 206-606-1320, mperciva@fredhutch.org
About this study
Official title: A Phase 1/2 Single-Center Trial Combining Venetoclax With G-CSF, Cladribine, Cytarabine, and Mitoxantrone (CLAG-M) for Patients With AML and High-Grade Myeloid Neoplasms
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.
Read the detailed description
OUTLINE:
This is a dose-escalation study of venetoclax.
Patients will receive induction with granulocyte colony-stimulating factor subcutaneously (SC) on days 0-5 (if peripheral white blood cell count is less than 20,000/uL), cladribine intravenously (IV) on days 1-5, cytarabine IV on days 1-5, and mitoxantrone IV 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.
After completion of study treatment, patients are followed up every 3 months for 12 months.
- Conditions
- Acute Biphenotypic Leukemia, Acute Myeloid Leukemia, Mixed Phenotype Acute Leukemia, Myeloid Neoplasm
- Being tested
- Cladribine, Cytarabine, Mitoxantrone, Recombinant Granulocyte Colony-Stimulating Factor, Venetoclax
- Medical subject headings
- Leukemia, Biphenotypic, Acute, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CladribineDrug
Also called 2-CdA, 2CDA, CdA, Cladribina
Given IV
CytarabineDrug
Also called .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
Given IV
MitoxantroneDrug
Also called Dihydroxyanthracenedione, Mitozantrone
Given IV
Recombinant Granulocyte Colony-Stimulating FactorBiological
Also called Recombinant Colony-Stimulating Factor 3, rhG-CSF
Given subcutaneously
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow aspiration
Bone Marrow BiopsyProcedure or surgery
Undergo bone marrow biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection
Undergo blood sample collection
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cladribine; Drug: Cytarabine; Drug: Mitoxantrone; Biological: Recombinant Granulocyte Colony-Stimulating Factor; Drug: Venetoclax; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Biospecimen Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events (Phase I)
Measured: Up to 12 months
Maximum tolerated dose of venetoclax in combination with CLAG-M (Phase I)
Measured: Up to 12 months
Event free survival (Phase II)
Measured: At 6 months
Secondary outcomes (4)
Complete remission rate
Measured: After 2 cycles (each cycle is approximately 35 days)
Rate of minimal residual disease negativity
Measured: Up to 1 year
Rate of allogeneic hematopoietic cell transplant
Measured: At 1 year
Overall survival
Measured: At 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2021
- Study start4 Feb 2022
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Biphenotypic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie
- Responsible party
- Sponsor
- Investigators
- Mary-Beth M. Percival, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04797767
- Sponsor's protocol ID
- RG1121403
- Other IDs
- NCI-2021-01379, 10793
- Status last verified
- Nov 2026
- First submitted
- 10 Mar 2021
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40535475
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Single-Center Trial Combining Venetoclax With G-CSF, Cladribine, Cytarabine, and Mitoxantrone (CLAG-M) for Patients With AML and High-Grade Myeloid Neoplasms
- ClinicalTrials.gov ID
- NCT04797767
- Acronym / sponsor ID
- RG1121403
- Conditions
- Acute Biphenotypic Leukemia, Acute Myeloid Leukemia, Mixed Phenotype Acute Leukemia, Myeloid Neoplasm
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- AbbVie
- Study start
- 4 Feb 2022 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 15 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OUTLINE:
This is a dose-escalation study of venetoclax.
Patients will receive induction with granulocyte colony-stimulating factor subcutaneously (SC) on days 0-5 (if peripheral white blood cell count is less than 20,000/uL), cladribine intravenously (IV) on days 1-5, cytarabine IV on days 1-5, and mitoxantrone IV 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.
After completion of study treatment, patients are followed up every 3 months for 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (CLAG-M, venetoclax) | Experimental | Drug: Cladribine, Drug: Cytarabine, Drug: Mitoxantrone, Biological: Recombinant Granulocyte Colony-Stimulating Factor, Drug: Venetoclax, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Procedure: Biospecimen CollectionPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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:
- PHASE II:
- Age >= 18 years
- Aspartate transaminase (AST) and alanine transaminase (ALT) =< 3.0 X upper limit of normal (ULN)
Key exclusion criteria (15 listed)
- Acute promyelocytic leukemia or chronic myeloid leukemia in 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CladribineAlso: 2-CdA, 2CDA, CdA, CladribinaGiven IV | Drug | Treatment (CLAG-M, venetoclax) |
| CytarabineAlso: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinoneGiven IV | Drug | Treatment (CLAG-M, venetoclax) |
| MitoxantroneAlso: Dihydroxyanthracenedione, MitozantroneGiven IV | Drug | Treatment (CLAG-M, venetoclax) |
| Recombinant Granulocyte Colony-Stimulating FactorAlso: Recombinant Colony-Stimulating Factor 3, rhG-CSFGiven subcutaneously | Biological | Treatment (CLAG-M, venetoclax) |
| VenetoclaxAlso: ABT-0199, ABT-199, ABT199, GDC-0199Given PO | Drug | Treatment (CLAG-M, venetoclax) |
| Bone Marrow AspirationUndergo bone marrow aspiration | Procedure or surgery | Treatment (CLAG-M, venetoclax) |
| Bone Marrow BiopsyUndergo bone marrow biopsy | Procedure or surgery | Treatment (CLAG-M, venetoclax) |
| Biospecimen CollectionAlso: Biological Sample CollectionUndergo blood sample collection | Procedure or surgery | Treatment (CLAG-M, venetoclax) |
Primary outcome
Incidence of adverse events (Phase I)
Time frame: Up to 12 months
Maximum tolerated dose of venetoclax in combination with CLAG-M (Phase I)
Time frame: Up to 12 months
Event free survival (Phase II)
Time frame: At 6 months
4 secondary outcomes
Complete remission rate
Time frame: After 2 cycles (each cycle is approximately 35 days)
Rate of minimal residual disease negativity
Time frame: Up to 1 year
Rate of allogeneic hematopoietic cell transplant
Time frame: At 1 year
Overall survival
Time frame: At 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Derived from this study: PubMed 40535475Raychaudhuri 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.
- Individual participant dataSharing planned: No
Related trials for Acute Biphenotypic Leukemia
Not yet recruitingPhase 1
A Study to Assess the Pharmacokinetics and Safety of Revumenib in Participants With Advanced Cancer and Hepatic or Renal Impairment
Relapsed/Refractory (R/R) Hematologic Malignancies, Acute Leukemia
RecruitingPhase 2
Personalized NK Cell Therapy in CBT
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Biphenotypic Leukemia
RecruitingPhase 1/2
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)
Acute Myeloid Leukemia, Acute Lymphoid Leukemia
RecruitingPhase 1
Prophylactic DLI-X for Leukemia Relapse After HCT
Acute Lymphoid Leukemia, Acute Myeloid Leukemia
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mary-Beth M. Percival principal investigator
Fred Hutch/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cladribine, Cytarabine and Mitoxantrone in people with Acute Biphenotypic Leukemia and Acute Myeloid Leukemia, run by University of Washington 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 18 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 6 Nov 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Kim Quach (206.606.8311, kquach@fredhutch.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (Phase I) (time frame: Up to 12 months). The study lists 3 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 NCT04797767, 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 6 Nov 2026.