AzTrials
AzTrials

Recurrent Acute Myeloid LeukemiaPhase 1NCT04375631

CLAG-M or FLAG-Ida Chemotherapy and Reduced-Intensity Conditioning Donor Stem Cell Transplant for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelomonocytic Leukemia

A Phase 1 study testing Cladribine, Cyclophosphamide and Cyclosporine in people with Recurrent Acute Myeloid Leukemia and Recurrent Chronic Myelomonocytic 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 trial studies the best dose of total body irradiation when given with cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M) or idarubicin, fludarabine, cytarabine and filgrastim (FLAG-Ida) chemotherapy reduced-intensity conditioning regimen before stem cell transplant in treating patients with… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cladribine, Cyclophosphamide and Cyclosporine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteUnited States
Study dates
3 Dec 2020to 17 Mar 2027
Phase
Phase 1
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

  • Age >= 18 years with an Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) =< 5 for patients over 60 years -(Enrollment of patients >= 75 years of age will require case presentation at the transplant Patient Care Conference (PCC) and approval by consensus)
  • Acute myeloid leukemia (AML) (2016 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 morphological 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, mixed phenotype acute leukemia) that is either primary refractory or is in untreated or unsuccessfully treated first or subsequent relapse are also eligible
  • Subjects with previously treated myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML), defined as prior treatment with at least one hypomethylating agent (HMA; azacitidine and/or decitabine) 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 or decitabine, 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
  • The use of hydroxyurea prior to initiation of study treatment is allowed. Patients with symptoms/signs of hyperleukocytosis, WBC > 100,000/uL or with concern for other complications of high tumor burden (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
  • Adequate cardiac function defined as absence of decompensated congestive heart failure and/or uncontrolled arrhythmia and left ventricular ejection fraction >= 45%
Show all 34Show fewer
  • 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 carbon monoxide diffusing capability test (DLCO) correct >= 70% mmHg or DLCO corrected 60-69% mmHg and partial pressure of oxygen (pO2) >= 70 mmHg
  • Serum creatinine =< 1.5 mg/dL
  • Prior autologous HCT is permissible if relapse occurred > 3 months but =< 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 or near-matched related, unrelated or haploidentical donor for collection of stimulated peripheral blood stem cells or HLA-matched or near-matched cord blood unit must be identified and readily available
  • Women of childbearing potential and men must agree to use adequate contraception beginning at the signing of the consent until at least 12 months post-transplant
  • Patients may have previously received chemotherapy with a mitoxantrone, idarubicin- or cladribine/fludarabine-based regimen for MDS or AML. If the patient has received CLAG-M or FLAG-Ida before and has been sensitive to this regimen, eligibility will be determined on a case-by-case basis by the study principal investigator (PI)
  • Ability to understand and sign a written informed consent document (or legal representative)
  • DONOR: Patients must have an HLA-matched related donor or an HLA-matched unrelated donor, or haploidentical donor who meets standard FHCC and/or National Marrow Donor Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) donation as follows:
  • 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
  • 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
  • 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
  • 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
  • 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.
  • Age ≥ 12 years
  • 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 available haploidentical donors, selection criteria should include, in this order:
  • For cytomegalovirus (CMV) seronegative recipients, a CMV seronegative donor
  • Red Blood Cell compatibility
  • i. RBC cross match compatible
  • ii. Minor ABO incompatibility
  • iii. Major ABO incompatibility

Who cannot join

  • Patients >= 18 years being treated at Seattle Children's Hospital
  • 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 anti-microbials 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
Show all 9Show fewer
  • Concurrent treatment with any other approved or investigational anti-leukemia agent
  • Haploidentical donor exclusion criteria:
  • 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.

Filippo Milano contact

206.667.5925

fmilano@fredhutch.org

United States1 site, 1 recruiting

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    Filippo Milano, 206-667-5925, fmilano@fredhutch.org

    Filippo Milano

    Recruiting

Other trials in United States

About this study

Official title: CLAG-M or FLAG-Ida Chemotherapy Followed Immediately by Related/Unrelated Reduced-Intensity Conditioning (RIC) Allogeneic Hematopoietic Cell Transplantation for Adults With Myeloid Malignancies at High Risk of Relapse: A Phase 1 Study

This phase I trial studies the best dose of total body irradiation when given with cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M) or idarubicin, fludarabine, cytarabine and filgrastim (FLAG-Ida) chemotherapy reduced-intensity conditioning regimen before stem cell transplant in treating patients with acute myeloid leukemia, myelodysplastic syndrome, or chronic myelomonocytic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Giving chemotherapy and total body irradiation before a donor peripheral blood stem cell 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 and may help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can attack the body's normal cells called graft versus host disease. Giving cyclophosphamide, cyclosporine, and mycophenolate mofetil after the transplant may stop this from happening.

Read the detailed description

OUTLINE: This a dose-escalation study of TBI. Patients are assigned to 1 of 2 arms.

ARM I: Patients receive filgrastim (G-CSF) subcutaneously (SC) daily on days -9 to -4, cladribine intravenously (IV) over 2 hours daily on days -8 to -4, cytarabine IV over 2 hours daily on days -8 to -4, and mitoxantrone IV over 60 minutes daily on days -8 to -6. If white blood cell (WBC) > 20,000/uL, filgrastim on days -9 and -8 may be omitted at physician discretion. Patients undergo TBI on either day -1 or 0 and HCT on day 0.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours daily on days 3-4, cyclosporine IV over 1-2 hours twice daily (BID) on days 5-60, and mycophenolate mofetil IV or orally (PO) BID on days 5-28 (transplant with related donors) or three times daily (TID) on days 5-35 (transplant with unrelated donors). After day 60, patients continue to receive cyclosporine tapered through day 180 at the discretion of the treating physician in the absence of GVHD.

ARM II: Patients receive G-CSF SC daily on days -9 to -4, fludarabine IV over 30 minutes daily on days -8 to -4, cytarabine IV over 2 hours daily on days -8 to -4, and idarubicin IV over 60 minutes daily on days -8 to -6. If white blood cell (WBC) > 20,000/uL, filgrastim on days -9 and -8 may be omitted at physician discretion. Patients undergo TBI on either day -1 or 0 and HCT on day 0. Patients receiving an unrelated cord blood (UCB) transplant also receive cyclophosphamide IV on day -2.

GVHD PROPHYLAXIS: Patients who received peripheral blood stem cell transplant receive cyclophosphamide IV over 1-2 hours daily on days 3-4, cyclosporine IV over 1-2 hours BID on days 5-60, and mycophenolate mofetil IV or PO BID on days 5-28 (transplant with related donors) or TID on days 5-35 (transplant with unrelated donors). After day 60, patients continue to receive cyclosporine tapered through day 180 at the discretion of the treating physician in the absence of GVHD. Patients who received an UCB transplant receive cyclosporine IV, over 1 hour, every 8 hours (Q8H) from day -3 until day +100 and mycophenolate mofetil IV or PO TID on days 5-35. After day 100 patients continue to receive cyclosporine tapered up to at least 6 months post-transplant.

Patients in both arms undergo multigated acquisition scan (MUGA) or echocardiography, and x-ray imaging during screening and as clinically indicated or per standard practice. Patients also undergo bone marrow biopsy and aspirate during screening, day 28, day 80 and at 1 year. Additionally, patients undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 100 days, at 6, 12, and 24 months post-transplant.

Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes, Leukemia, Biphenotypic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CladribineDrug

    Also called 2-CdA, 2CDA, CdA, Cladribina

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • CyclosporineDrug

    Also called 27-400, Ciclosporin, CsA, Cyclosporin

    Given IV then PO

  • 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

  • FilgrastimBiological

    Also called G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

    Given SC

  • Hematopoietic Cell TransplantationProcedure or surgery

    Also called HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant

    Undergo HCT

  • MitoxantroneDrug

    Also called Dihydroxyanthracenedione, Mitozantrone

    Given IV

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given IV or PO

  • Mycophenolate SodiumDrug

    Also called ERL 080, ERL 080A, Socium Mycophenolate

    Given PO

  • Total-Body IrradiationRadiation

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

    Undergo TBI

  • IdarubicinDrug

    Also called 4-DMDR

    Given IV

  • FludarabineDrug

    Also called Fluradosa, 9-Beta-D-arabinofuranosyl-2-fluoroadenine

    Given IV

  • CytarabineDrug

    Also called WR-28453, U-19920, Udicil

    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

  • Echocardiography TestProcedure or surgery

    Also called EC

    Undergo ECHO

  • X-Ray ImagingProcedure or surgery

    Also called Conventional X-Ray, Diagnostic Radiology, Medical Imaging

    Undergo x-ray

  • Bone Marrow BiopsyProcedure or surgery

    Undergo bone marrow biopsy and aspirate

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy and aspirate

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection

    Undergo blood sample collection

Study groups in NCT04375631
Study groupRoleWhat they receive
Arm I (CLAG-M, TBI, HCT, GVHD prophylaxis)ExperimentalSee detailed description.
Receives: Drug: Cladribine; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Cytarabine; Biological: Filgrastim; Procedure: Hematopoietic Cell Transplantation; Drug: Mitoxantrone; Drug: Mycophenolate Mofetil; Drug: Mycophenolate Sodium; Radiation: Total-Body Irradiation; Procedure: Multigated Acquisition Scan; Procedure: Echocardiography Test; Procedure: X-Ray Imaging; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Biospecimen Collection
Arm II (FLAG-Ida, TBI, HCT, GVHD prophylaxis)ExperimentalSee detailed description.
Receives: Drug: Cyclophosphamide; Drug: Cyclosporine; Procedure: Hematopoietic Cell Transplantation; Drug: Mycophenolate Mofetil; Drug: Mycophenolate Sodium; Radiation: Total-Body Irradiation; Drug: Idarubicin; Drug: Fludarabine; Drug: Cytarabine; Procedure: Multigated Acquisition Scan; Procedure: Echocardiography Test; Procedure: X-Ray Imaging; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Biospecimen Collection

What is being measured

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

  1. Rate of hematopoietic cell transplantation (HCT) failure

    Defined as graft rejection (< 5% donor T-cell chimerism).

    Measured: Within 200 days post-transplant

  2. Rate of disease progression

    Defined by European LeukemiaNet (ELN) 2017 criteria and International Working Group (IWG).

    Measured: Within 200 days post-transplant

Secondary outcomes (5)

  1. Incidence of adverse events

    Measured: Up to 100 days post-transplant

  2. Rates of stem cell engraftment and donor chimerism

    Measured: At 80 days (+/- 7 days)

  3. Rates of grades II-IV acute graft versus host disease (GVHD) and chronic GVHD requiring systemic immunosuppressive treatment

    Measured: Up to 2 years

  4. Disease response

    Measured: Up to 2 years

  5. 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 posted5 May 2020
  2. Study start3 Dec 2020
  3. Primary completion28 Feb 2027 (estimated)
  4. Study completion17 Mar 2027 (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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04375631
Sponsor's protocol ID
RG1006914
Other IDs
NCI-2020-02616, RG1006914, P30CA015704, 10457
Status last verified
Sep 2026
First submitted
1 May 2020
Last updated
17 Sep 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 study testing Cladribine, Cyclophosphamide and Cyclosporine in people with Recurrent Acute Myeloid Leukemia and Recurrent Chronic Myelomonocytic 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 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 17 Sep 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 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.

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 (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?

Rate of hematopoietic cell transplantation (HCT) failure (time frame: Within 200 days post-transplant). 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 NCT04375631.

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 17 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in