Venetoclax in Combination With Cladribine and Cytarabine Alternating With Azacitidine Plus Venetoclax for the Treatment of Newly Diagnosed Monocytic AML and Active Signaling Mutated AML

NCT06504459 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: STUDY00026216NCI-2024-05084
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests how well venetoclax with cladribine and cytarabine alternating with azacitidine and venetoclax works in treating patients with newly diagnosed monocytic acute myeloid leukemia (AML) and active signaling mutated AML. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It 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 azacitidine, 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 cladribine and cytarabine alternating with azacitidine and venetoclax may kill more cancer cells in patients with newly diagnosed monocytic AML and active signaling mutated AML.

Conditions

Acute Monocytic Leukemia; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Composite complete remission (CRc) rate

  CRc is defined as achievement of complete remission (CR), CR with partial hematologic recovery (CRh) or CR with incomplete blood count recovery (CRi) after induction (or re-induction). The CRc rate will be computed on the safety set and presented with a point-estimate and exact binomial 95% confidence interval (CI). CRc will also be modeled with univariable logistic regressions, applied to the efficacy set, to determine if any baseline patient or disease feature is correlated with clinical response.

  At start of treatment to post-induction disease assessment (Cycle 1 Day 21 or Cycle 2 Day 21. Each cycle is 28 days)

Secondary Outcomes (6)

• Overall response rate (ORR)

  At start of treatment to post-induction disease assessment (Cycle 1 Day 21 or Cycle 2 Day 21. Each cycle is 28 days)

• Overall survival (OS)

  At start of treatment to death up to 2 years

• Event-free survival (EFS)

  At start of treatment to primary refractory disease, hematologic relapse, discontinuation of treatment due to toxicity, disease progression or death up to 2 years

• Duration of response (DOR)

  At first date of documented ≥ MLFS or better to primary refractory disease, hematologic relapse, discontinuation of treatment due to toxicity, disease progression or death up to 2 years

• Incidence of grade ≥ 3 adverse events (AEs)

  At start of treatment up to 30 days after last dose of any study drug

Study Arms (1)

Treatment (venetoclax, cladribine, cytarabine, azacitidine)

EXPERIMENTAL

See Detailed Description

Drug: Azacitidine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cladribine; Drug: Cytarabine; Procedure: Echocardiography; Procedure: Lumbar Puncture; Procedure: Multigated Acquisition Scan; Other: Questionnaire Administration; Drug: Venetoclax

Interventions

Azacitidine DRUG

Given IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (venetoclax, cladribine, cytarabine, azacitidine)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (venetoclax, cladribine, cytarabine, azacitidine)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (venetoclax, cladribine, cytarabine, azacitidine)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (venetoclax, cladribine, cytarabine, azacitidine)

Cladribine DRUG

Given IV

Also known as: 2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251

Treatment (venetoclax, cladribine, cytarabine, azacitidine)

Cytarabine DRUG

Given SC

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 (venetoclax, cladribine, cytarabine, azacitidine)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (venetoclax, cladribine, cytarabine, azacitidine)

Lumbar Puncture PROCEDURE

Undergo LP

Also known as: LP, Spinal Tap

Treatment (venetoclax, cladribine, cytarabine, azacitidine)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (venetoclax, cladribine, cytarabine, azacitidine)

Questionnaire Administration OTHER

Ancillary studies

Treatment (venetoclax, cladribine, cytarabine, azacitidine)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (venetoclax, cladribine, cytarabine, azacitidine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to comprehend the investigational nature of the study and provide informed consent (i.e., participant or legally authorized representative \[LAR\]). Written informed consent must be obtained prior to any study-specific procedures or interventions
• Sign informed consent for the #4422 Biorepository prior to any study-specific procedures of interventions
• Eligible AML patients of all races and ethnic groups will be considered for participation, irrespective of gender identity
• Newly diagnosed, histologically confirmed monocytic AML, as defined by World Health Organization (WHO), or active signaling mutated AML defined as AML with mutation(s) to N/KRAS, FLT3 ITD/TKD, NF1, PTPN11 or CBL
• Ineligible for standard of care induction therapy using intensive chemotherapy (IC) or unwilling to undergo IC induction therapy. Ineligible for IC is defined as
• ≥ 75 yrs of age; OR
• yrs of age with one of the following:
• Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2 at screening
• Severe cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
• Severe pulmonary disorder (e.g., diffuse capacity of the lung for carbon monoxide \[DLCO\] ≤ 65% or forced expiratory volume in 1 second \[FEV1\] ≤ 65%)
• Creatinine clearance \< 45 ml/min (calculated by the Cockcroft-Gault equation)
• Hepatic disorder with total bilirubin \> 1.5 x upper limit of normal (ULN)
• Any other comorbidity that the treating physician judges to be incompatible with IC
• If ≥ 75 yrs of age, the following organ function values must be met and ECOG must be 0 to 2 at screening:
• Creatinine clearance (calculated with the Cockcroft-Gault equation) ≥ 30 ml/min

You may not qualify if:

• Symptomatic central nervous system involvement with AML
• Prior treatment for AML, with the exception of cytoreduction for proliferative disease (per institutional protocol) with any of the following: Hydroxyurea, hematopoietic growth factors, leukapheresis
• Another active malignancy within the previous 5 years of C1D1
• Investigational therapy within 28 days of C1D1, or within 5 half-lives or longer, if known
• Hypersensitivity to any of the components of the investigational regimen (i.e., cladribine, cytarabine, venetoclax, azacitidine) or any excipients in the formulations
• Treatment based on agents targeting or inhibiting BCL-2 (for other, prior indication/malignancy) within the previous 5 years
• History of dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
• Use of drugs with documented drug-drug interaction toxicities with the study drugs
• Uncontrolled infection. Participants with controlled infection must be afebrile and hemodynamically stable for at least 72 hours prior to C1D1 and must be amenable to alternate treatment if current treatment will interact with investigational regimen
• Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Enrollment of individuals with evidence of chronic HBV or HCV infection will be considered on a case-by-case basis by the principal investigator
• Individuals with serology positive for human immunodeficiency virus (HIV) and under active treatment with highly active antiretroviral therapy (HAART) (or another therapy that may interfere with metabolism of study agents)
• Pregnancy at enrollment or unwillingness to stop breastfeeding. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding be discontinued from start of treatment until 1 week after the final dose of any study drug
• Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, unstable cardiac or pulmonary function or acute insufficiency (e.g., symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia), or psychiatric illness or social situation that could limit compliance with study requirements

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator
• AbbVie: collaborator

Study Sites (2)

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

RECRUITING

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute

Interventions

Azacitidine; Specimen Handling; Biopsy; Cladribine; Cytarabine; Spinal Puncture; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyadenosines; Deoxyribonucleosides; Arabinonucleosides; Diagnostic Techniques, Neurological; Punctures; Therapeutics

Study Officials

• Curtis A Lachowiez

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 16, 2024
• Study Start: January 3, 2025
• Primary Completion (Estimated): October 11, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (2)