Combination Chemotherapy (FLAG-Ida) Followed Immediately by Reduced-Intensity Total Body Radiation Therapy and Donor Hematopoietic Cell Transplant for the Treatment of Adults Age 60 and Older With Newly Diagnosed Adverse-Risk Acute Myeloid Leukemia or Other High-Grade Myeloid Cancer

NCT07046078 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1125246NCI-2025-02981FHIRB0020835
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests the safety, side effects, and how well combination chemotherapy with fludarabine, high-dose cytarabine, granulocyte colony-stimulating factor (G-CSF), and idarubicin (FLAG-Ida) followed immediately by reduced-intensity total body radiation therapy, called total body irradiation (TBI), and donor hematopoietic cell transplant (HCT) works in treating adults age 60 and older with newly diagnosed adverse-risk acute myeloid leukemia (AML) or other high-grade myeloid cancer. Despite advances in supportive care and the approval of more than 10 new drugs since 2017, the outcomes of older adults with adverse-risk acute myeloid leukemia and other high-grade myeloid cancers remains poor. Most patients are expected to die from their cancer or the consequences of treatment-related side effects. Donor HCT is a very important part of any curative-cancer treatment for these patients. However, while accepted as standard care for decades, this treatment exposes patients to long periods of drug-induced low blood cell counts and the problems associated with low blood counts, like infections and bleeding, which are associated with significant risk of chronic side effects and death. This study will use a different approach to the upfront curative-cancer treatment of older adults with an adverse-risk AML or other high-grade myeloid cancer. This study will use intense chemotherapy followed a few days later by lower-dose TBI and donor HCT. Chemotherapy drugs, such as idarubicin, fludarabine, high-dose cytarabine 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. G-CSF helps the bone marrow make more white blood cells in patients with low white blood cell count due to cancer treatment. This approach allows effective treatment of cancer cells and overall reduction of the period of low blood cells counts. This decreases the risk for problems associated with low blood counts, such as infection and chronic side effects. Decreasing these are important for older adults who undergo HCT. This treatment strategy may improve treatment outcomes by allowing more patients to successfully undergo donor HCT and reduce the risk of low blood cell counts and the problems associated with low blood counts. Giving chemotherapy followed immediately by reduced-intensity TBI and donor HCT may be safe, tolerable and/or effective in treating adults age 60 and older with newly diagnosed adverse-risk AML or other high-grade myeloid cancer.

Conditions

Acute Leukemia of Ambiguous Lineage; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Proportion of participants starting study treatment with FLAG-Ida within 42 days of the date of informed consent

  Will evaluate the proportion of participants starting study treatment with FLAG-Ida within 42 days of the date of informed consent.

  Up to 42 days after informed consent

Secondary Outcomes (16)

• Number of patients transplanted

  Up to 2 years

• Time from day of consent to day of allogeneic hematopoietic cell transplant (HCT)

  From day of consent to day of allogeneic hematopoietic cell transplant (HCT)

• Reasons for failure to undergo allogeneic transplantation (allo-HCT)

  Up to 2 years following Screening enrollment

• Incidence of adverse events

  From start of conditioning (Day -9) to study-defined neutrophil engraftment, or adversely, to graft failure

• Neutrophil count recovery

  Day 0 to study-defined neutrophil engraftment, or adversely, to graft failure.

Study Arms (1)

Treatment (FLAG-Ida, TBI, HCT)

EXPERIMENTAL

Patients receive granulocyte colony-stimulating factor SC QD on days -9 to -4 or days -7 to -4 as clinically indicated, fludarabine IV over 30 minutes QD on days -8 to -4, cytarabine IV over 2 hours QD on days -8 to -4, and idarubicin IV over 60 minutes QD on days -8 to -6. Patients undergo TBI QD on days -1 and 0 or BID on day -1 or 0. Patients then undergo allogeneic HCT with unmodified peripheral blood stem cells IV on day 0 or 1 day after TBI as clinically indicated. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MUGA or ECHO during screening and as clinically indicated, undergo bone marrow biopsy and/or aspiration throughout the study and blood sample collection during follow up.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Procedure: Echocardiography Test; Drug: Fludarabine; Drug: Idarubicin; Procedure: Multigated Acquisition Scan; Biological: Peripheral Blood Stem Cell; Other: Questionnaire Administration; Biological: Recombinant Granulocyte Colony-Stimulating Factor; Radiation: Total-Body Irradiation

Interventions

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and/or aspiration

Treatment (FLAG-Ida, TBI, HCT)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and/or aspiration

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

Treatment (FLAG-Ida, TBI, HCT)

Cytarabine DRUG

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 (FLAG-Ida, TBI, HCT)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (FLAG-Ida, TBI, HCT)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (FLAG-Ida, TBI, HCT)

Idarubicin DRUG

Given IV

Also known as: 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin, 4-DMDR

Treatment (FLAG-Ida, TBI, HCT)

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, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (FLAG-Ida, TBI, HCT)

Peripheral Blood Stem Cell BIOLOGICAL

Given IV

Also known as: PBSC, Peripheral Blood Stem Cells, peripheral stem cell, Peripheral Stem Cells

Treatment (FLAG-Ida, TBI, HCT)

Questionnaire Administration OTHER

Ancillary studies

Treatment (FLAG-Ida, TBI, HCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: SCT_TBI, TBI, Total Body Irradiation, Whole Body, Whole Body Irradiation, Whole-Body Irradiation

Treatment (FLAG-Ida, TBI, HCT)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic HCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (FLAG-Ida, TBI, HCT)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (FLAG-Ida, TBI, HCT)

Recombinant Granulocyte Colony-Stimulating Factor BIOLOGICAL

Given SC

Also known as: Recombinant Colony-Stimulating Factor 3, rhG-CSF

Treatment (FLAG-Ida, TBI, HCT)

Eligibility Criteria

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

You may qualify if:

• PARTICIPANTS: Age ≥ 60 years. Adults age \< 60 years are eligible if they are felt to be unsuitable candidates for myeloablative conditioning as per physician assessment
• PARTICIPANTS: Ability to understand and willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of potential study participants
• PARTICIPANTS: Newly diagnosed, untreated high-risk myeloid or mixed myeloid/lymphoid neoplasm:
• Adverse-risk AML (using 2022 International Consensus Classification for disease categorization and 2022 European LeukemiaNet \[ELN\] criteria for molecular/cytogenetic risk assignment)
• Acute leukemia of ambiguous lineage (using 2022 International Consensus Classification for disease categorization)
• High-risk myelodysplastic neoplasm (MDS) (Molecular International Prognostic System \[IPSS-M\] moderate high, high, or very high, OR ≥ 10% blasts in blood or marrow)
• High-risk chronic myelomonocytic leukemia (CMML) (clinical/molecular CMML-specific prognostic scoring system \[CPSS-Mol\] intermediate-2 or high, OR ≥ 10% blasts in blood or marrow)
• Prior treatment of MDS or CMML with lower-intensity therapy (e.g., growth factors, erythropoiesis-stimulating agents, and lenalidomide) is permissible, but patients may not have received prior hypomethylating agents
• PARTICIPANTS: Disease not requiring immediate anti-neoplastic therapy (e.g., presenting with leukopenia or pancytopenia), defined as a clinical scenario in which delay of systemic leukemia-directed treatment would be unsafe. Supportive cytoreduction with hydroxyurea for transient disease control is allowed, and does not constitute immediate anti-neoplastic treatment
• PARTICIPANTS: Interest in pursuing allogeneic HCT
• PARTICIPANTS: Available caregiver
• PARTICIPANTS: Karnofsky score ≥ 70; Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• PARTICIPANTS: Bilirubin ≤ 2.5 x institutional upper limit of normal unless elevation is thought to be due to hepatic infiltration by myeloid neoplasm, Gilbert's syndrome, or hemolysis
• PARTICIPANTS: Serum creatinine ≤ 1.5 mg/dL
• PARTICIPANTS: Prior autologous HCT is permissible if \> 6 months after planned HCT on this study

You may not qualify if:

• PARTICIPANTS: Active central nervous system (CNS) disease
• PARTICIPANTS: Decompensated congestive heart failure and/or uncontrolled arrhythmia and/or significant medical history of cardiac disease precluding allogeneic HCT
• PARTICIPANTS: Significant medical history of pulmonary disease and/or symptoms suggestive of pulmonary disease precluding allogeneic HCT
• PARTICIPANTS: Treatment with any other approved or investigational anti-leukemia agent(s) at the time of initiation of study treatment
• PARTICIPANTS: Concomitant illness associated with a likely survival of \< 1 year
• PARTICIPANTS: Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with antimicrobials and/or controlled or stable. Patients with fever thought to be secondary to myeloid malignancy are eligible
• PARTICIPANTS: Known hypersensitivity or contraindication to receiving any of the study drugs used in this trial, including post-transplant cyclophosphamide (PTCy)
• PARTICIPANTS: Pregnancy or lactation
• PARTICIPANTS: Psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

Stem Cell Transplantation; Specimen Handling; Biopsy; Cytarabine; fludarabine; Idarubicin; Peripheral Blood Stem Cell Transplantation; pegylated granulocyte colony-stimulating factor; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Hematopoietic Stem Cell Transplantation; Radiotherapy

Study Officials

• Filippo Milano, MD, PhD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Filippo Milano, MD, PhD

CONTACT

206-667-5925; fmilano@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2025
• First Posted: July 1, 2025
• Study Start: September 26, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2029
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)