Phase 1/2 FLAG-IDA, VEN and Asciminib in CML and Ph+ AML

June 4, 2026 updated by: M.D. Anderson Cancer Center

Phase Ib/II of the Combination of Fludarabine, Cytarabine, Idarubicin, G-CSF (FLAG-Ida) With Venetoclax and Asciminib in Patients With Advanced Phase Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia

The goal of Phase 1b is to establish the safety of asciminib in combination with FLAG-Ida and venetoclax in patients with CML-MBP, CML-LBP, and Ph+ AML. The goal of Phase 2 is to learn if asciminib in combination with FLAG-Ida and venetoclax can help to control the disease.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Primary Objectives:

Phase 1: To establish the safety of asciminib in combination with FLAG-Ida and venetoclax.

Phase 2: To evaluate the efficacy and toxicity of asciminib in combination with FLAG-Ida and venetoclax.

Primary Endpoints:

Phase 1: Incidence of dose limiting toxicities (DLTs) during the first cycle of study treatment.

Phase 2: Rate of complete response and rate of adverse events.

Secondary Objectives:

To assess the rates of conversion to CML-CP with this combination. To assess the cytogenetic and molecular response rates with this combination. To assess the survival outcomes with this combination.

Secondary Endpoints:

Rate of conversion to CML-CP defined as CR/CRi/CRh. Rates of CCyR, MMR, MR4, and MR4.5. Relapse-free survival (RFS) and overall survival.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • UT MD Anderson
        • Contact:
        • Principal Investigator:
          • Fadi Haddad, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 to 70 years. Because no dosing or adverse event data are currently available on the use of the combination of FLAG-Ida with venetoclax and asciminib in patients <18 years of age, children are excluded from this study.

  • Newly diagnosed or relapsed/refractory:

    • BCR::ABL1-rearranged CML in myeloid BP or Philadelphia chromosomepositive or BCR::ABL1-rearranged AML as defined by the WHO 2022 criteria23
    • BCR::ABL1-rearranged CML in lymphoid BP.
  • ECOG performance status ≤ 2.

  • Adequate liver, cardiac, renal and pancreatic function as defined by the following criteria:

    • Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis, or the underlying leukemia approved by the Principal Investigator (PI)
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3 x ULN, unless due to the underlying leukemia approved by the PI
    • Creatinine clearance ≥ 30 mL/min
    • Serum amylase or lipase ≤ 1.5 x ULN
    • Left ventricular ejection fraction ≥ 40%.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

  • Because the therapeutic agents used in this trial could potentially be teratogenic, women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. This includes all female patients, up until the age of 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:

    • Postmenopausal (no menses in greater than or equal to 12 consecutive months)
    • History of hysterectomy or bilateral salpingo-oophorectomy
    • Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy)
    • History of bilateral tubal ligation or another surgical sterilization procedure.
  • Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of trial treatment
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Patients who are receiving any other investigational agents used for the treatment of other cancers.
  • Patients who have progressed on asciminib and/or a combination of intensive chemotherapy plus venetoclax. Patients with prior treatment with a hypomethylating agent and venetoclax will be eligible.
  • Active grade III-V cardiac failure as defined by the New York Heart Association Criteria.
  • Myocardial infarction, unstable angina, or stroke within 3 months prior to signing informed consent.
  • Clinically significant atrial or ventricular arrhythmias (such as uncontrolled, clinically significant atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) as determined by the treating physician.
  • Prolonged QTcF interval on pre-entry electrocardiogram (> 470 msec) unless corrected after electrolyte replacement or approved by a cardiologist.
  • History of acute pancreatitis within 6 months or medical history of chronic pancreatitis.
  • Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment).
  • Active secondary malignancy that in the investigator's opinion will shorten survival to less than one year.
  • Treatment with any investigational antileukemic agent in the last 14 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator. Prior recent treatment with corticosteroids, hydroxyurea, cytarabine (up to 2 g/m2 given for cytoreduction within the preceding 7 days) and/or an FDA-approved BCR::ABL1 TKI is permitted.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the combination of FLAG-Ida, venetoclax, asciminib, or blinatumomab.
  • Pregnant women are excluded from this study because study drugs have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study drugs, breastfeeding should be discontinued.
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment with FLAG-Ida + Venetoclax + Asciminib
Drug: Fludarabine
Given by IV
Other Names:
  • Fludara
Drug: Cytarabine
Given by IV
Other Names:
  • cytosine arabinoside
Drug: Idarubicin
Given by IV
Other Names:
  • Idamycin and Idamycin PFS
Drug: Filgrastim
Given by injection
Other Names:
  • Neupogen
  • Zarxio
Drug: Venetoclax
Given by orally
Other Names:
  • Venclexta
Drug: Asciminib
Given orally
Other Names:
  • Scemblix
Experimental: Treatment with FLAG-Ida + Venetoclax + Asciminib + Blinatumomab
Drug: Fludarabine
Given by IV
Other Names:
  • Fludara
Drug: Blinatumomab
Given by IV
Other Names:
  • Blincyto
Drug: Cytarabine
Given by IV
Other Names:
  • cytosine arabinoside
Drug: Idarubicin
Given by IV
Other Names:
  • Idamycin and Idamycin PFS
Drug: Filgrastim
Given by injection
Other Names:
  • Neupogen
  • Zarxio
Drug: Venetoclax
Given by orally
Other Names:
  • Venclexta
Drug: Asciminib
Given orally
Other Names:
  • Scemblix

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Adverse Events (AEs)
Time Frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 6.0
Through study completion; an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Investigators

  • Principal Investigator: Fadi Haddad, MD, UT MD Anderson

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 30, 2026

Primary Completion (Estimated)

June 3, 2031

Study Completion (Estimated)

June 3, 2033

Study Registration Dates

First Submitted

May 18, 2026

First Submitted That Met QC Criteria

May 18, 2026

First Posted (Actual)

May 22, 2026

Study Record Updates

Last Update Posted (Actual)

June 8, 2026

Last Update Submitted That Met QC Criteria

June 4, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-1873
  • NCI-2026-03869 (Other Identifier: NCI-CTRP Clinical Trials Registry)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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