Acute Leukemia of Ambiguous LineagePhase 2NCT07046078
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
A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Biospecimen Collection and Bone Marrow Aspiration in people with Acute Leukemia of Ambiguous Lineage and Acute Myeloid Leukemia, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Leukemia of Ambiguous Lineage, Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia
- What is being tested?
- Allogeneic Hematopoietic Stem Cell Transplantation, Biospecimen Collection and Bone Marrow Aspiration
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Sep 2025to 30 Jun 2029
- Phase
- Phase 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
- 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)
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- 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
- PARTICIPANTS: Participants of child-bearing potential must be willing to employ two highly effective and acceptable forms of contraception 7 days before initiation of study treatment and for at least 12 months after HCT. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during screening (within 2 weeks of treatment initiation, per Fred Hutch Cancer Center [FHCC] standard of care [SOC]), where WOCBP are defined as all female participants between 18-55 years of age, unless postmenopausal or with hysterectomy
- PARTICIPANTS: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- PARTICIPANTS: 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. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
- PARTICIPANTS: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen, as determined by the investigator, are eligible for this trial
- DONORS: Patients must have an HLA-matched related donor, an HLA-matched or mismatched unrelated donor, or an HLA- haploidentical donor who meets standard Fred Hutchinson Cancer Center (FHCC) and/or National Marrow Donor Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) donation as follows:
- HLA-matched related donor: related to the patient and genotypically or phenotypically identical for HLA-A, B, C, DRB1 and DQB1. Phenotypic identity must be confirmed by high-resolution typing
- HLA-matched unrelated donor:
- 10/10 matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing
- Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment. The recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT. If the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained. The donor should be excluded if any of the cytotoxic cross match assays are positive. A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion
- HLA-mismatched unrelated donor:
- HLA-matching must be based on results of high resolution typing at HLA-A, -B, -C, -DRB1, and -DQ
- Mismatched for a single allele without antigen mismatching at HLA-A, B, or C as defined by high resolution typing but otherwise matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing
- HLA class I HLA-A, -B, -C allele matched donors allowing for any one or two DRB1 and/or DQB1 antigen/allele mismatch
- Donor/recipient HLA mismatching at loci for which the patient is homozygous is not allowed (isolated rejection vector)
- HLA-haploidentical donor:
- Donors must be haploidentical relatives of the patients. Donor-recipient compatibility will be tested through HLA typing at high resolution for the HLA loci (-A, -B, -C, -DRB1, -DQB1). Donor and recipient should share at least 5/10 HLA loci
- Donor age ≥ 12 years
- Donor weight ≥ 40 kg
- Ability of donors younger than 18 years of age to undergo apheresis without use of a vascular access device. Vein check must be performed and verified by an apheresis nurse prior to arrival
- Donor must meet the selection criteria as defined by the Foundation of the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) guidelines
- In case of more than one available haploidentical donor, preference should be given to younger age
- Since detection of anti-donor-specific antibodies (anti-DSA) is associated with higher graft rejection rate, patients will be screened for anti-DSA pre-transplant. Use of donors requiring desensitization treatment of the patient are not permissible
Who cannot join
- 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
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- 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
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
Filippo Milano, MD, PhD, 206-667-5925, fmilano@fredhutch.org
Filippo Milano, MD, PhD
About this study
Official title: Pilot Study of FLAG-Ida Followed Immediately by Reduced-Intensity Allogeneic HCT for Adults Age 60 and Older With Newly Diagnosed Adverse-Risk AML or Other High-Grade Myeloid Neoplasm
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.
Read the detailed description
OUTLINE:
Patients receive granulocyte colony-stimulating factor subcutaneously (SC) once daily (QD) on days -9 to -4 or days -7 to -4 as clinically indicated, fludarabine intravenously (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 twice daily (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 multigated acquisition scan (MUGA) or echocardiography (ECHO) during screening and as clinically indicated, undergo bone marrow biopsy and/or aspiration throughout the study and blood sample collection during follow up.
After completion of study treatment, patients are followed up at days 28, 56 and 80, at months 3 and 6 and at years 1 and 2.
- Conditions
- Acute Leukemia of Ambiguous Lineage, Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome
- Being tested
- Allogeneic Hematopoietic Stem Cell Transplantation, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Cytarabine
- Medical subject headings
- Leukemia, Biphenotypic, Acute, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC
Undergo allogeneic HCT
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow biopsy and/or aspiration
Bone Marrow BiopsyProcedure or surgery
Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow
Undergo bone marrow biopsy and/or aspiration
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
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
FludarabineDrug
Also called Fluradosa
Given IV
IdarubicinDrug
Also called 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin, 4-DMDR
Given IV
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA
Peripheral Blood Stem CellBiological
Also called PBSC, Peripheral Blood Stem Cells, peripheral stem cell, Peripheral Stem Cells
Given IV
Questionnaire AdministrationOther
Ancillary studies
Recombinant Granulocyte Colony-Stimulating FactorBiological
Also called Recombinant Colony-Stimulating Factor 3, rhG-CSF
Given SC
Total-Body IrradiationRadiation
Also called SCT_TBI, TBI, Total Body Irradiation, Whole Body
Undergo TBI
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 42 days after informed consent
Secondary outcomes (16)
Number of patients transplanted
Will evaluate the number of patients transplanted.
Measured: Up to 2 years
Time from day of consent to day of allogeneic hematopoietic cell transplant (HCT)
Will evaluate time from day of consent to day of allogeneic HCT.
Measured: From day of consent to day of allogeneic hematopoietic cell transplant (HCT)
Reasons for failure to undergo allogeneic transplantation (allo-HCT)
Identified reasons for failure to undergo allogeneic transplantation (e.g., lack of suitable donor, complications of disease) will be systematically categorized and quantitatively reported.
Measured: Up to 2 years following Screening enrollment
Incidence of adverse events
Will evaluate the number of participants with non-hematologic adverse events ≥ grade 3. Will use the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for toxicity and adverse event reporting.
Measured: From start of conditioning (Day -9) to study-defined neutrophil engraftment, or adversely, to graft failure
Neutrophil count recovery
Will evaluate the time to neutrophil count recovery. The day of neutrophil recovery will be the 1st day of 2 consecutive days of absolute neutrophil count at or above 500/µL.
Measured: Day 0 to study-defined neutrophil engraftment, or adversely, to graft failure.
Platelet count recovery
Will evaluate the time to platelet count recovery. Platelet engraftment will be defined as the first of 7 days of a platelet count > 20,000/µl without subsequent transfusions for 7 days.
Measured: Day 0 to study-defined platelet engraftment
Incidence of severe adverse events
Will evaluate the number of participants with any severe adverse event. Will use the NCI CTCAE version 5.0 for toxicity and adverse event reporting.
Measured: From start of conditioning (Day -9) to study-defined neutrophil engraftment, or adversely, to graft failure
Non-relapse mortality (NRM)
Will evaluate the number of participants experiencing NRM by day +100 after HCT.
Measured: Up to day 100 after HCT
Rate of CD3 chimerism
Will evaluate the rate of peripheral blood CD3 chimerism at day 80 (±7 days). Mixed or full donor chimerism will be evidence of donor engraftment.
Full chimerism: > 95% donor CD3+ T cells. Mixed chimerism: the detection of peripheral blood donor T cells (CD3+) and granulocytes (CD33+) as a proportion of the total peripheral blood T cell and granulocyte population, respectively.
Measured: At day 80 (+/- 7 days)
Rate of CD33 chimerism
Will evaluate the rate of peripheral blood CD33 chimerism at day 80 (±7 days). Mixed or full donor chimerism will be evidence of donor engraftment. Full chimerism: > 95% donor CD3+ T cells. Mixed chimerism: the detection of peripheral blood donor T cells (CD3+) and granulocytes (CD33+) as a proportion of the total peripheral blood T cell and granulocyte population, respectively.
Measured: At day 80 (+/- 7 days)
Incidence of acute graft versus host disease (GVHD)
Will evaluate the cumulative incidence of grade 2-4 acute GVHD by day +100.
Measured: Up to day 100
Incidence of chronic GVHD
Will evaluate the cumulative incidence of chronic GVHD requiring systemic immunosuppressive therapy by day +365.
Measured: Up to day 365
Number of participants achieving complete remission or complete remission with incomplete hematologic recovery by day +42
Will evaluate the number of participants achieving complete remission or complete remission with incomplete hematologic recovery by day +42. Will be determined by peripheral blood count and bone marrow evaluation and categorized according to the 2022 European LeukemiaNet criteria.
Measured: Up to day 42
Measurable ("minimal") residual disease (MRD)-negativity
Will evaluate the number of participants achieving MRD-negativity by day +42. Will be determined by peripheral blood count and bone marrow evaluation and categorized according to the 2022 European LeukemiaNet criteria.
Measured: Up to day 42
Relapse-free survival
Will evaluate relapse-free survival at day +180. Will be determined by peripheral blood count and bone marrow evaluation and categorized according to the 2022 European LeukemiaNet criteria.
Measured: At day 180
Overall survival
Will evaluate overall survival at day +180.
Measured: At day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2025
- Study start26 Sep 2025
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Leukemia of Ambiguous LineageStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Filippo Milano, MD, PhD, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07046078
- Sponsor's protocol ID
- RG1125246
- Other IDs
- NCI-2025-02981, FHIRB0020835
- Status last verified
- Jul 2026
- First submitted
- 4 Jun 2025
- Last updated
- 20 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of FLAG-Ida Followed Immediately by Reduced-Intensity Allogeneic HCT for Adults Age 60 and Older With Newly Diagnosed Adverse-Risk AML or Other High-Grade Myeloid Neoplasm
- ClinicalTrials.gov ID
- NCT07046078
- Acronym / sponsor ID
- RG1125246
- Conditions
- Acute Leukemia of Ambiguous Lineage, Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Study start
- 26 Sep 2025 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 1 Jul 2025 (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 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.
Detailed description
OUTLINE:
Patients receive granulocyte colony-stimulating factor subcutaneously (SC) once daily (QD) on days -9 to -4 or days -7 to -4 as clinically indicated, fludarabine intravenously (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 twice daily (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 multigated acquisition scan (MUGA) or echocardiography (ECHO) during screening and as clinically indicated, undergo bone marrow biopsy and/or aspiration throughout the study and blood sample collection during follow up.
After completion of study treatment, patients are followed up at days 28, 56 and 80, at months 3 and 6 and at years 1 and 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (FLAG-Ida, TBI, HCT) | Experimental | 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 IrradiationPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- 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:
- 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
Key exclusion criteria (9 listed)
- 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
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 |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell TransplantationAlso: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSCUndergo allogeneic HCT | Procedure or surgery | Treatment (FLAG-Ida, TBI, HCT) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Treatment (FLAG-Ida, TBI, HCT) |
| Bone Marrow AspirationUndergo bone marrow biopsy and/or aspiration | Procedure or surgery | Treatment (FLAG-Ida, TBI, HCT) |
| Bone Marrow BiopsyAlso: Biopsy of Bone Marrow, Biopsy, Bone MarrowUndergo bone marrow biopsy and/or aspiration | Procedure or surgery | Treatment (FLAG-Ida, TBI, HCT) |
| 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 (FLAG-Ida, TBI, HCT) |
| Echocardiography TestAlso: EC, EchocardiographyUndergo ECHO | Procedure or surgery | Treatment (FLAG-Ida, TBI, HCT) |
| FludarabineAlso: FluradosaGiven IV | Drug | Treatment (FLAG-Ida, TBI, HCT) |
| IdarubicinAlso: 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin, 4-DMDRGiven IV | Drug | Treatment (FLAG-Ida, TBI, HCT) |
| Multigated Acquisition ScanAlso: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool ScanUndergo MUGA | Procedure or surgery | Treatment (FLAG-Ida, TBI, HCT) |
| Peripheral Blood Stem CellAlso: PBSC, Peripheral Blood Stem Cells, peripheral stem cell, Peripheral Stem CellsGiven IV | Biological | Treatment (FLAG-Ida, TBI, HCT) |
| Questionnaire AdministrationAncillary studies | Other | Treatment (FLAG-Ida, TBI, HCT) |
| Recombinant Granulocyte Colony-Stimulating FactorAlso: Recombinant Colony-Stimulating Factor 3, rhG-CSFGiven SC | Biological | Treatment (FLAG-Ida, TBI, HCT) |
| Total-Body IrradiationAlso: SCT_TBI, TBI, Total Body Irradiation, Whole BodyUndergo TBI | Radiation | Treatment (FLAG-Ida, TBI, HCT) |
Primary outcome
Proportion of participants starting study treatment with FLAG-Ida within 42 days of the date of informed consent
Time frame: Up to 42 days after informed consent
Will evaluate the proportion of participants starting study treatment with FLAG-Ida within 42 days of the date of informed consent.
16 secondary outcomes
Number of patients transplanted
Time frame: Up to 2 years
Time from day of consent to day of allogeneic hematopoietic cell transplant (HCT)
Time frame: From day of consent to day of allogeneic hematopoietic cell transplant (HCT)
Reasons for failure to undergo allogeneic transplantation (allo-HCT)
Time frame: Up to 2 years following Screening enrollment
Incidence of adverse events
Time frame: From start of conditioning (Day -9) to study-defined neutrophil engraftment, or adversely, to graft failure
Neutrophil count recovery
Time frame: Day 0 to study-defined neutrophil engraftment, or adversely, to graft failure.
Platelet count recovery
Time frame: Day 0 to study-defined platelet engraftment
Incidence of severe adverse events
Time frame: From start of conditioning (Day -9) to study-defined neutrophil engraftment, or adversely, to graft failure
Non-relapse mortality (NRM)
Time frame: Up to day 100 after HCT
Rate of CD3 chimerism
Time frame: At day 80 (+/- 7 days)
Rate of CD33 chimerism
Time frame: At day 80 (+/- 7 days)
Incidence of acute graft versus host disease (GVHD)
Time frame: Up to day 100
Incidence of chronic GVHD
Time frame: Up to day 365
Number of participants achieving complete remission or complete remission with incomplete hematologic recovery by day +42
Time frame: Up to day 42
Measurable ("minimal") residual disease (MRD)-negativity
Time frame: Up to day 42
Relapse-free survival
Time frame: At day 180
Overall survival
Time frame: At day 180
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 20 Jul 2026.
- Individual participant dataSharing planned: No
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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.
Filippo Milano, MD, PhD 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 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Biospecimen Collection and Bone Marrow Aspiration in people with Acute Leukemia of Ambiguous Lineage and Acute Myeloid Leukemia, run by Fred Hutchinson Cancer Center 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 37 inclusion and 9 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 20 Jul 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 phase mean?
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 Filippo Milano, MD, PhD (206-667-5925, fmilano@fredhutch.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants starting study treatment with FLAG-Ida within 42 days of the date of informed consent (time frame: Up to 42 days after informed consent). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Jul 2026.