AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 2NCT04994808

Treosulfan-Based Versus Clofarabine-Based Conditioning Before Donor Hematopoietic Stem Cell Transplant for the Treatment of Myelodysplastic Syndromes or Acute Myeloid Leukemia

A Phase 2 study testing Clofarabine, Fludarabine and Hematopoietic Cell Transplantation in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Fred Hutchinson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This phase II trials studies the effect of treosulfan-based versus clofarabine-based conditioning regimens before donor hematopoietic stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Clofarabine, Fludarabine and Hematopoietic Cell Transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
11 Aug 2023to 16 Jul 2026
Phase
Phase 2
Are there results?
None posted in the registry

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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >= 18 years and =< 75 years
  • Diagnosis of MDS-EB or AML: must have < 5% marrow blasts (by morphology and/or flow cytometry) at time of transplant
  • Karnofsky performance score (KPS) >= 60% on pre-HCT evaluation
  • Able to give informed consent
  • Patients with previous autologous or allogeneic HCT may enroll
  • DONOR: Human leukocyte antigen (HLA)-identical related donors or unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 as defined by high resolution deoxyribonucleic acid (DNA) typing; mismatch for only one HLA allele at class I is allowed
  • DONOR: Donors able to undergo peripheral blood stem cell collection. Only granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell (PBSC) will be permitted as an hematopoietic stem cell (HSC) source on this protocol

Who cannot join

  • Presence of circulating blasts (in the blood) detected by standard pathology for patients with AML
  • Presence of >= 5% circulating leukemic blasts (in the blood) detected by standard pathology for patients with MDS-EB
  • Patients with promyelocytic AML
  • Organ dysfunction
  • Cardiac: Ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%) or cardiac insufficiency requiring treatment or symptomatic coronary artery disease. Patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist
  • Pulmonary:
Show all 26Show fewer
  • Diffusion capacity of the lung for carbon monoxide (DLCO) < 40%, total lung capacity (TLC) < 40%, forced expiratory volume in 1 second (FEV1) < 40% and/or receiving supplementary continuous oxygen. When pulmonary function test (PFT)s cannot be obtained, the 6-minute walk test (6 minute walk functional test [6MWT], also known as exercise oximetry) will be used: Any patient with oxygen saturation on room air of < 89% during a 6MWT will be excluded
  • The principal investigator (PI) must approve enrollment of all patients with pulmonary nodules
  • Renal: Serum creatinine should be within normal limits as specified by Standard Practice guidelines. For subjects with serum creatinine > upper limit of normal, a 24-hour creatinine clearance will be performed and should be equal to or more than the lower limit of normal
  • Hepatic: Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension. Patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease
  • With active infectious disease requiring deferral of conditioning, as recommended by an infectious disease specialist
  • Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
  • With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis because of possible risk of lethal infection when treated with immunosuppressive therapy
  • With central nervous system (CNS) leukemia at the time of treatment
  • Patients with active non-hematologic malignancies (except non-melanoma skin cancers) or those with non-hematologic malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease but have a greater than 20% chance of having disease recurrence within five years. This exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
  • With life expectancy severely limited by diseases other than malignancy
  • Fertile men and women unwilling to used contraceptive techniques during treatment and for 12 months following
  • Women who are pregnant or lactating
  • With known hypersensitivity to treosulfan, fludarabine, or clofarabine
  • The use of non-Food and Drug Administration (FDA) approved investigational drugs would not be allowed within 4 weeks of the initiation of conditioning (day -6 for both arms)
  • Unable to give informed consent
  • Patients suitable for and willing to receive a standard high intensity preparative regimen
  • DONOR: Donor (or centers) who will exclusively donate marrow
  • DONOR: Donors who are HIV-positive and/or, medical conditions that would result in increased risk for G-CSF mobilization and harvest of PBSC
  • DONOR: Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment. This determination is based on the standard practice of the individual institution. The recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a 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 cross match is an absolute donor exclusion
  • DONOR: Donor is excluded if a patient is homozygous in the graft-rejection vector against the donor's mismatched HLA class I allele

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase II Randomized Study to Assess Outcomes With Treosulfan-Based Versus Clofarabine-Based Conditioning in Patients With Myelodysplastic Syndromes With Excess Blasts (MDS-EB), or Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Cell Transplantation (HCT)

This phase II trials studies the effect of treosulfan-based versus clofarabine-based conditioning regimens before donor hematopoietic stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia. Chemotherapy drugs, such as treosulfan, fludarabine, and clofarabine, 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. Giving chemotherapy and total-body irradiation before a donor hematopoietic 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. This study may help doctors determine whether treosulfan-based or clofarabine-based conditioning regimen works better before donor hematopoietic stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia.

Read the detailed description

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive treosulfan intravenously (IV) over 2 hours on days -6 to -4 and fludarabine IV over 30 minutes on days -6 to -2. Patients also undergo total-body irradiation (TBI) followed by HCT on day 0. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and lumbar puncture pre-transplant and undergo bone marrow aspiration, bone marrow biopsy, and collection of blood samples at pre-transplant and post-transplant.

ARM B: Patients receive clofarabine IV over 2 hours on days -6 to -2. Patients also undergo TBI followed by HCT on day 0. Patients undergo ECHO or MUGA and lumbar puncture pre-transplant and undergo bone marrow aspiration, bone marrow biopsy, and collection of blood samples at pre-transplant and post-transplant.

After completion of study intervention, patients are followed up at days 28, 56, 84 and 180, years 1 and 1.5 and then annually for 5 years.

Being tested
Clofarabine, Fludarabine, Hematopoietic Cell Transplantation, Total-Body Irradiation, Treosulfan
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

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

  • ClofarabineDrug

    Also called Clofarex, Clolar

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Hematopoietic Cell TransplantationProcedure or surgery

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

    Undergo HCT

  • Total-Body IrradiationRadiation

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

    Undergo TBI

  • TreosulfanDrug

    Also called 1,2,3, 4-Butanetetrol, 1,4-dimethanesulfonate, [R-(R*,S*)]-, Dihydroxybusulfan, Ovastat, Trecondi

    Given IV

  • Echocardiography TestProcedure or surgery

    Also called EC

    Undergo ECHO

  • Multigated Acquisition ScanProcedure or surgery

    Also called MUGA, MUGA Scan, Multi-Gated Acquisition Scan

    Undergo MUGA

  • Lumbar PunctureProcedure or surgery

    Also called LP, spinal tap

    Undergo lumbar puncture

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Undergo bone marrow biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection

    Undergo collection of blood samples

Study groups in NCT04994808
Study groupRoleWhat they receive
Arm A (treosulfan, fludarabine, TBI, HCT)ExperimentalPatients receive treosulfan IV over 2 hours on days -6 to -4 and fludarabine IV over 30 minutes on days -6 to -2. Patients also undergo TBI followed by HCT on day 0. Patients undergo ECHO or MUGA and lumbar puncture pre-transplant and undergo bone marrow aspiration, bone marrow biopsy, and collection of blood samples at pre-transplant and post-transplant.
Receives: Drug: Fludarabine; Procedure: Hematopoietic Cell Transplantation; Radiation: Total-Body Irradiation; Drug: Treosulfan; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Lumbar Puncture; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Biospecimen Collection
Arm B (clofarabine, TBI, HCT)ExperimentalPatients receive clofarabine IV over 2 hours on days -6 to -2. Patients also undergo TBI followed by HCT on day 0. Patients undergo ECHO or MUGA and lumbar puncture pre-transplant and undergo bone marrow aspiration, bone marrow biopsy, and collection of blood samples at pre-transplant and post-transplant.
Receives: Drug: Clofarabine; Procedure: Hematopoietic Cell Transplantation; Radiation: Total-Body Irradiation; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Lumbar Puncture; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Biospecimen Collection

What is being measured

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

  1. Relapse-free survival

    Measured: At 6 months after transplant

Secondary outcomes (5)

  1. Overall survival

    Measured: At 1 year after transplant

  2. Rate of non-relapse mortality

    Measured: At 1 year after transplant

  3. Relapse rate

    Measured: At 1 year after transplant

  4. Incidence of acute graft versus host disease

    Measured: At 1 year after transplant

  5. Duration of hospitalization

    Measured: Up to day 100 post hematopoietic stem cell transplantation

Timeline

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

  1. First posted6 Aug 2021
  2. Study start11 Aug 2023
  3. Primary completion22 Jan 2026
  4. Study completion16 Jul 2026

Why it stopped: The study was closed due to the end of funding.

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04994808
Sponsor's protocol ID
RG1121616
Other IDs
NCI-2021-07474, 10598
Status last verified
Aug 2026
First submitted
29 Jul 2021
Last updated
6 Aug 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 2 study testing Clofarabine, Fludarabine and Hematopoietic Cell Transplantation in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, 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 7 inclusion and 26 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: stopped early, as of the sponsor's last update on 6 Aug 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?

The study was stopped early (reason given: The study was closed due to the end of funding.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Relapse-free survival (time frame: At 6 months after transplant). 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 NCT04994808.

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 6 Aug 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