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Acute Myeloid LeukemiaPhase 1/2NCT06928662

Chemotherapy (Decitabine in Combination With FLAG-Ida) and Total-Body Irradiation Followed by Donor Stem Cell Transplant for the Treatment of Adults With Myeloid Malignancies at High Risk of Relapse

A Phase 1/2 study testing Decitabine, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Acute Myeloid Leukemia and Acute Undifferentiated Leukemia, run by Fred Hutchinson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase I/II trial studies the safety, side effects, and best dose of decitabine in combination with fludarabine, cytarabine, filgrastim, and idarubicin (FLAG-Ida) and total body irradiation (TBI) followed by a donor stem cell transplant in treating adult patients with cancers of blood-forming cells of the bone… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
Decitabine, Bone Marrow Aspiration and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
23 Sep 2025to 29 Nov 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
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years with an HCT-co-morbidity index (CI) ≤ 5 for patients over 60 years.
  • AML (2022 World Health Organization [WHO] criteria) that is either primary refractory (as defined by failure of 2 cycles of 7+3-like chemotherapy, 1 cycle of high-dose cytarabine-based chemotherapy, or at least 2 cycles of venetoclax in combination with other therapies) or is in untreated or unsuccessfully treated first or subsequent relapse. Patients in morphologic remission (i.e. < 5% blasts in the bone marrow) but evidence of minimal residual disease (MRD) by multiparameter flow cytometry, cytogenetics/fluorescence in situ hybridization (FISH), or molecular means will be eligible for trial participation. Patients with relapsed or refractory acute leukemia of ambiguous lineage (acute undifferentiated leukemia or mixed phenotype acute leukemia) that is either primary refractory or is in untreated or unsuccessfully treated first or subsequent relapse are also eligible.
  • MDS and CMML: Subjects with previously treated MDS and CMML, defined as prior treatment with at least one hypomethylating agent (hypomethylating agent [HMA]; azacitidine, decitabine and/or decitabine-cedazuridine) whose disease progressed, relapsed, or was refractory to HMA treatment as follows: 1) patients who have failed at least 4 cycles of monotherapy with azacitidine, decitabine or decitabine-cedazuridine, 2) patients who received at least 2 cycles of HMA in combination with another therapeutic agent. Subjects with MDS and CMML who failed at least 1 cycle of induction chemotherapy will be also eligible. Patients with MDS or CMML who progress to secondary AML will be eligible if they received at least 4 cycles of HMA alone or 2 cycles of HMA in combination with another therapeutic agent.
  • Patients may have previously received hypomethylating agents or chemotherapy with a mitoxantrone, idarubicin- or cladribine/fludarabine-based regimen for MDS or AML. If the patient has received cladribine-cytarabine-filgrastim-mitoxantrone (CLAG-M) or FLAG-Ida before and has been sensitive to this regimen, defined as MRD negative complete remission (CR) immediately after receiving the treatment and which lasts ≥ 1 year, eligibility will be determined on a case-by-case basis by the study principal investigator (PI).
  • The use of hydroxyurea prior to initiation of study treatment is allowed. Patients with symptoms/signs of hyperleukocytosis, white blood cells (WBC) > 100,000/μL or with concern for other complications of high tumor burden of high tumor dynamics (e.g. disseminated intravascular coagulation) can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2 per dose) prior to start of study treatment.
  • Karnofsky score ≥ 70; Eastern Cooperative Oncology Group (ECOG) 0-1.
Show all 34Show fewer
  • Adequate cardiac function defined as absence of decompensated congestive heart failure and/or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 45%.
  • Bilirubin ≤ 2.5 x Institutional Upper Limit of Normal unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis
  • Adequate pulmonary function defined as absence of oxygen (O2) requirements and either diffusion capacity of the lung for carbon monoxide (DLCO) corrected ≥ 70%mmHg or DLCO corrected 60-69%mmHg and partial pressure of oxygen (pO2) ≥ 70mmHg.
  • Creatinine clearance > 60 mL/min.
  • Prior autologous HCT is permissible if relapse occurred > 6 months after HCT.
  • Prior TBI-containing allogeneic HCT up to 3 Gy is permissible if > 6 months after HCT.
  • A human leukocyte antigen (HLA)-matched sibling/unrelated donor, mismatched unrelated donor or haploidentical donor for collection of stimulated peripheral blood stem cells must be identified and readily available.
  • Ability to understand and sign a written informed consent document (or legal representative).
  • SIBLING 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.
  • MATCHED UNRELATED DONOR: Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR 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.
  • MATCHED UNRELATED DONOR: 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. For those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results. A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion.
  • MATCHED UNRELATED DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed.
  • MISMATCHED UNRELATED DONOR: HLA-matching must be based on results of high resolution typing at HLA-A, -B, -C, -DRB1, and -DQ.
  • MISMATCHED UNRELATED DONOR: Mismatch for one HLA class I antigen with or without an additional mismatch for one HLA-class I allele but matched for HLA-DRB1 and HLA-DQ.
  • MISMATCHED UNRELATED DONOR: Mismatched for two HLA class I alleles but matched for HLA-DRB1 and HLA-DQ.
  • MISMATCHED UNRELATED DONOR: HLA class I HLA-A, -B, -C allele matched donors allowing for any one or two DRB1 and/or DQB1 antigen/allele mismatch.
  • MISMATCHED UNRELATED DONOR: If the patient is homozygous at the mismatch HLA class I locus or II locus, the donor must be heterozygous at that locus and one allele must match the patient (i.e., patient is homozygous A*01:01 and donor is heterozygous A*01:01, A*02:01). This mismatch will be considered a one-antigen mismatch for rejection only.
  • 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.
  • HAPLOIDENTICAL DONOR: Age ≥ 18 years.
  • HAPLOIDENTICAL DONOR: Weight ≥ 40 kg.
  • HAPLOIDENTICAL DONOR: 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.
  • DONOR: In case of more available donors, selection criteria should include, in this order:
  • For cytomegalovirus (CMV) seronegative recipients, a CMV seronegative donor
  • Red Blood Cell compatibility
  • Red blood cell (RBC) cross match compatible
  • Minor ABO incompatibility
  • Major ABO incompatibility
  • DONOR: Donors will undergo diagnostic evaluation (clinical, laboratory test and imaging) as indicated per institutional guidelines.

Who cannot join

  • Active central nervous system (CNS) disease.
  • Concomitant illness associated with a likely survival of < 1 year.
  • 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 likely secondary to myeloid malignancy are eligible.
  • Known hypersensitivity or contraindication to any study drug used in this trial.
  • Pregnancy or lactation.
  • Concurrent treatment with any other approved or investigational anti-leukemia agent.
  • HAPLOIDENTICAL DONOR: 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. Patient with DSA mean fluorescent intensity (MFI) < 5000 after desensitization treatment, will be considered eligible to participate in the study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Naveed Ali, MD contact

206-667-5854

nali2@fredhutch.org

United States1 site, 1 recruiting

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    Naveed Ali, MD, 206-667-5854, nali2@fredhutch.org

    Naveed Ali, MD

    Recruiting

Other trials in United States

About this study

Official title: Sequential Decitabine in Combination With FLAG-Ida Followed Immediately by Reduced-Intensity Conditioning (RIC) Allogeneic Hematopoietic Cell Transplantation (DEC-FLAG-Ida/RIC) for Adults With Myeloid Malignancies at High Risk of Relapse: A Phase 1/2 Study

This phase I/II trial studies the safety, side effects, and best dose of decitabine in combination with fludarabine, cytarabine, filgrastim, and idarubicin (FLAG-Ida) and total body irradiation (TBI) followed by a donor stem cell transplant in treating adult patients with cancers of blood-forming cells of the bone marrow (myeloid malignancies) that are at high risk of coming back after treatment (relapse). Cancers eligible for this trial are acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myelomonocytic leukemia (CMML). Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. The FLAG-Ida regimen consists of the following drugs: fludarabine, cytarabine, filgrastim, and idarubicin. These are chemotherapy drugs that 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. Filgrastim is in a class of medications called colony-stimulating factors. It works by helping the body make more neutrophils, a type of white blood cell. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. TBI is radiation therapy to the entire body. Giving chemotherapy and TBI before a donor peripheral blood stem cell (PBSC) transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets. Giving decitabine in combination with FLAG-Ida and TBI before donor PBSC transplant may work better than FLAG-Ida and TBI alone in treating adult patients with myeloid malignancies at high risk of relapse.

Read the detailed description

OUTLINE: This is a phase I, dose-escalation study of decitabine in combination with FLAG-Ida, TBI, and HCT followed by a phase II study.

DONORS: Participants undergo apheresis for collection of PBSCs on study.

PATIENTS: Patients receive decitabine intravenously (IV) daily over 1 hour on days -12 to -10, -14 to -10, -16 to -10, or -19 to -10, filgrastim subcutaneously (SC) daily on days -9 to -4, idarubicin IV over 60 minutes daily on days -8 to -6, fludarabine IV over 30 minutes daily on days -8 to -4, cytarabine IV over 2 hours daily on days -8 to -4, and undergo TBI twice daily (BID) on day -1 or 0 OR daily on days -1 and 0 in the absence of disease progression or unacceptable toxicity. Patients then undergo HCT (receive donor PBSCs via infusion) on day 0. Patients also undergo multi-gated acquisition (MUGA) scan or echocardiography (ECHO) during screening, chest X-rays and bone marrow aspiration and/or biopsy during screening and as clinically indicated, and collection of blood samples throughout the study.

After completion of study treatment, patients are followed up at 6 months, 1 year, and 2 years.

Being tested
Decitabine, Bone Marrow Aspiration, Bone Marrow Biopsy, Chest Radiography, Cytarabine
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Biphenotypic, 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.

  • DecitabineDrug

    Also called 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine

    Given IV

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration and/or biopsies

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow aspiration and/or biopsies

  • Chest RadiographyProcedure or surgery

    Also called Chest X-ray

    Undergo chest X-rays

  • 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

  • FilgrastimBiological

    Also called Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi

    Given SC

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Hematopoietic Cell TransplantationProcedure or surgery

    Also called HCT, Hematopoietic Stem Cell Infusion, HEMATOPOIETIC STEM CELL TRANSPLANT, Hematopoietic Stem Cell Transplantation

    Given via infusion

  • 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

  • PheresisProcedure or surgery

    Also called Apheresed, Apheresis, Blood Component Removal, Collection, Apheresis/Leukapheresis

    Undergo apheresis

  • Total-Body IrradiationRadiation

    Also called SCT_TBI, TBI, Total Body Irradiation, Whole Body

    Undergo TBI

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood

Study groups in NCT06928662
Study groupRoleWhat they receive
Treatment (decitabine, FLAG-Ida, HCT)ExperimentalDONORS: Participants undergo apheresis for collection of PBSCs on study. PATIENTS: Patients receive decitabine IV daily over 1 hour on days -12 to -10, -14 to -10, -16 to -10, or -19 to -10, filgrastim SC daily on days -9 to -4, idarubicin IV over 60 minutes daily on days -8 to -6, fludarabine IV over 30 minutes daily on days -8 to -4, cytarabine IV over 2 hours daily on days -8 to -4, and undergo TBI BID on day -1 or 0 OR daily on days -1 and 0 in the absence of disease progression or unacceptable toxicity. Patients then undergo HCT (receive donor PBSCs via infusion) on day 0. Patients also undergo MUGA scan or ECHO during screening, chest X-rays and bone marrow aspiration and/or biopsy during screening and as clinically indicated, and collection of blood samples throughout the study.
Receives: Drug: Decitabine; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Chest Radiography; Drug: Cytarabine; Procedure: Echocardiography Test; Biological: Filgrastim; Drug: Fludarabine; Procedure: Hematopoietic Cell Transplantation; Drug: Idarubicin; Procedure: Multigated Acquisition Scan; Procedure: Pheresis; Radiation: Total-Body Irradiation; Procedure: Biospecimen Collection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Non-relapse mortality (Phase 1)

    Will evaluate whether intensification of fludarabine, cytarabine, filgrastim, and idarubicin/reduced intensity conditioning with the potential sequential addition of 4 escalating doses of decitabine prior to allografting with 4 Gy total-body irradiation would be feasible with an acceptable rate of toxicity and non-relapse mortality within the first 100 days following allograft, where day -100 non-relapse mortality is meant to encompass various measures of "toxicity".

    Measured: At day 100

  2. Disease-free survival (Phase 2)

    Measured: At 1 year

Secondary outcomes (6)

  1. Rate of stem cell engraftment (Phase 1)

    Will use exploratory, descriptive, and observational methods to 1) estimate the rates of stem cell engraftment.

    Measured: Up to day 80

  2. Rate of donor chimerism (Phase 1)

    Will use exploratory, descriptive, and observational methods to estimate donor chimerism.

    Measured: Up to day 80

  3. Rates of grades II-IV acute graft-versus-host disease (GVHD) (Phase 1)

    Will use exploratory, descriptive, and observational methods to estimate the rates of grades II-IV acute GVHD requiring systemic immunosuppressive treatment.

    Measured: Up to 2 years

  4. Rates of grades II-IV chronic GVHD (Phase 1)

    Will use exploratory, descriptive, and observational methods to estimate the rates of grades II-IV chronic GVHD requiring systemic immunosuppressive treatment.

    Measured: Up to 2 years

  5. Disease response (Phase 1)

    Will use exploratory, descriptive, and observational methods to estimate disease response.

    Measured: Up to 2 years

  6. Duration of remission (Phase 1)

    Will use exploratory, descriptive, and observational methods to estimate duration of remission.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2025
  2. Study start23 Sep 2025
  3. Primary completion9 Mar 2028 (estimated)
  4. Study completion29 Nov 2028 (estimated)

Resources

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
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06928662
Sponsor's protocol ID
RG1125142
Other IDs
NCI-2025-01992, FHIRB0020797
Status last verified
May 2026
First submitted
8 Apr 2025
Last updated
15 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Decitabine, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Acute Myeloid Leukemia and Acute Undifferentiated 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 34 inclusion and 7 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 15 May 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 Naveed Ali, MD (206-667-5854, nali2@fredhutch.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Non-relapse mortality (Phase 1) (time frame: At day 100). The study lists 2 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 NCT06928662.

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 15 May 2026.

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