AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 2NCT03121014

Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) in Addition to Fludarabine/Busulfan Conditioning for Allogeneic Transplantation in High Risk AML and Myelodysplastic Syndromes

A Phase 2 study testing Fludarabine, Busulfan and ATG in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by University of Illinois Chicago at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The study is a Phase II clinical trial. Patients will receive intensity modulated total marrow irradiation (TMI) at a dose of 9 Gy with standard myeloablative fludarabine/ i.v. targeted busulfan (FluBu) conditioning prior to allogeneic hematopoietic stem cell transplant (HSCT). Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Fludarabine, Busulfan and ATG
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteUnited States
Study dates
24 Apr 2017to Nov 2026
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 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18-65 years
  • Patients with AML or MDS who meet the following criteria:
  • Relapsed or refractory AML (including AML in CR2)
  • Poor-risk AML in first remission, with remission defined as <5% bone marrow blasts morphologically:
  • AML arising from MDS or a myeloproliferative disorder, or secondary AML
  • Poor risk molecular features including presence of FLT3 internal tandem duplication mutation.
Show all 18Show fewer
  • Poor-risk cytogenetics: Monosomal karyotype, complex karyotype (> 3 abnormalities), inv(3), t(3;3), t(6;9), MLL rearrangement with the exception of t(9;11), or abnormalities of chromosome 5 or 7
  • Primary refractory disease
  • MDS with at least one of the following poor-risk features:
  • Poor-risk cytogenetics including 3q abnormalities, 7/7q minus or complex cytogenetics (>3 abnormalities)
  • Current or previous INT-2 or high IPSS score
  • Treatment-related MDS
  • MDS diagnosed before age 21 years
  • Progression on or lack of response to standard DNA-methyltransferase inhibitor therapy
  • Life-threatening cytopenias, including those requiring regular PRBC or platelet transfusions e. CML with a history of accelerated or blast phase
  • Patients must have a related or unrelated peripheral blood stem cell donor as follows:
  • Sibling donor must be a 6/6 match for HLA-A, -B at intermediate (or higher) resolution and -DRB1 at high resolution using DNA based typing
  • Unrelated donors must be at least 7/8 match at HLA-A, -B, -C and DRB1 at high resolution using DNA-based typing

Who cannot join

  • Presence of significant co morbidity as shown by:
  • Left ventricular ejection fraction < 50%
  • Creatinine clearance <30ml/min
  • Bilirubin > 2.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST > 5 x ULN
  • FEV1 and FVC < 50% of predicted or DLCO <50% of predicted once corrected for anemia
  • Karnofsky score <70 (appendix C)
Show all 23Show fewer
  • Hematopoietic cell transplantation comorbidity index >3
  • Active viral hepatitis or HIV infection
  • Cirrhosis
  • Pregnancy
  • Patients unable to sign informed consent
  • Patient who have previously received radiation to >20% of bone marrow containing areas.
  • 4. DONOR ELIGIBILITY AND SELECTION
  • 4.1. Donor Selection
  • Donor evaluation and selection is by standard for normal clinical practice. No study procedures are to be performed on donors. All donors must be willing to donate peripheral blood stem cells and meet institutional or NMDP criteria for donation.
  • The following prioritization will be used when selecting donors:
  • When possible, an HLA compatible sibling will be used as a donor.
  • For patients who do not have an HLA compatible sibling, an unrelated donor will be used
  • 8/8 matched unrelated donors are preferred over single antigen mismatched donors.
  • If more than one potential volunteer unrelated donor is considered suitable further selection of the most suitable donor is at the discretion of the treating physician. The following serves only as a guide for prioritization:
  • Age of donor (18-24 > 25-34 > 35-44 > 45+)
  • Sex and parity of donor (male > female, nulliparous female > parous, multiparous female)
  • Cytomegalovirus (CMV) status, if recipient is CMV seronegative (CMV- > CMV+)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Illinois at Chicago

    Chicago, Illinois, 60612

Other trials in United States

About this study

Official title: A Phase II Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) in Addition to Fludarabine/Busulfan Conditioning for Allogeneic Transplantation in High Risk AML and Myelodysplastic Syndromes

The study is a Phase II clinical trial. Patients will receive intensity modulated total marrow irradiation (TMI) at a dose of 9 Gy with standard myeloablative fludarabine/ i.v. targeted busulfan (FluBu) conditioning prior to allogeneic hematopoietic stem cell transplant (HSCT).

Read the detailed description

Patients will receive the following conditioning regimen: fludarabine 40 mg/m2 IVBP daily for day -5 (5 days before stem cell infusion) through Day -2, IV busulfan targeting a 4800μM/min/ day from day -5 through day -2, and ATG (Thymoglobulin®) at 0.5 mg/kg IV on day -3, and 2 mg/kg on days -2 and day -1 (Only for recipients of stem cells from unrelated or mismatched donors). In addition to the above conditioning regimen all patients will receive TMI at a dose of 3Gy on days -3, -2 and -1. On day 0, the stem cell product will be infused according to BMT unit policy. Graft versus host disease (GVHD) prophylaxis will consist of administration of tacrolimus and methotrexate (see Section 8). Post-transplant evaluation will be done as per standard care with study data collected at day 30, 60, 90, 180, 365 and 2 years.

Being tested
Fludarabine, Busulfan, ATG, Total Marrow Irradiation, Stem Cell Product Infusion
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.

  • FludarabineDrug

    Also called Fludara®

    40 mg/m^2 IVBP daily for day -5 (5 days before stem cell infusion) through Day -2

  • BusulfanDrug

    Also called Busulfex®

    targeting a 4800μM/min/ day from day -5 through day -2

  • ATGDrug

    Also called Thymoglobulin®

    0.5 mg/kg IV on day -3, and 2 mg/kg on days -2 and day -1

  • Total Marrow IrradiationRadiation

    dose of 3Gy on days -3, -2 and -1

  • Stem Cell Product InfusionProcedure or surgery

    Day 0 according to BMT unit policy

  • TacrolimusDrug

    Also called FK-506, Prograf®

    The starting dose is at 0.03 mg/kg/day IV continuous infusion over 24 hr from 4 PM on day -2. Dose will be adjusted to target trough levels of 5-15 ng/mL. More information is available in the protocol document.

  • MethotrexateDrug

    Also called Trexall®

    5mg/m^2 on Day 1, 5 mg/m^2 on Days 3, 6 and 11

Study groups in NCT03121014
Study groupRoleWhat they receive
Patient TreatmentExperimentalPatients will receive fludarabine 40 mg/m2 IVBP daily for day -5 (5 days before stem cell infusion) through Day -2, IV busulfan targeting a 4800μM/min/ day from day -5 through day -2, and ATG (Thymoglobulin®) at 0.5 mg/kg IV on day -3, and 2 mg/kg on days -2 and day -1 (Only for recipients of stem cells from unrelated or mismatched donors). In addition to the above conditioning regimen all patients will receive TMI at a dose of 3Gy on days -3, -2 and -1. On day 0, the stem cell product will be infused according to BMT unit policy. Graft versus host disease (GVHD) prophylaxis will consist of administration of tacrolimus and methotrexate. Post-transplant evaluation will be done as per standard care with study data collected at day 30, 60, 90, 180, 365 and 2 years.
Receives: Drug: Fludarabine; Drug: Busulfan; Drug: ATG; Radiation: Total Marrow Irradiation; Procedure: Stem Cell Product Infusion; Drug: Tacrolimus; Drug: Methotrexate

What is being measured

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

  1. Relapse free survival of approximately 30% in high-risk patients conditioned with the Fludarabine/ Busulfan regimen

    Using a Simon 2 stage optimal design with α of 0.05 and power of 0.8, 15 patients will be enrolled in the first stage. If greater than 5 patients survive to 1 year without relapse the study will continue into stage 2. Recruitment will then continue to a total of 46 patients. In this expanded cohort, if a total of 18 or more patients survive to 1 year without relapse, the treatment will be judged efficacious and worthy of further study.

    Measured: Up to 1 year

Secondary outcomes (3)

  1. Relapse free survival

    It will be estimated and reported with 90% confidence intervals. The proportion of patients who are alive at 1-year will also be estimated with a 90% exact binomial confidence interval.

    Measured: Up to 1 year

  2. Overall survival

    It will be estimated and reported with 90% confidence intervals. The proportion of patients who are alive at 1-year will also be estimated with a 90% exact binomial confidence interval.

    Measured: Up to 1 year

  3. Transplant related mortality rate

    After accrual of 10 patients, analysis will be performed to ensure that the mortality rate does not exceed 30%. By calculation of confidence intervals to ensure the TRM not exceed 30%, accrual would be halted if n= 6 of 10 (lower bound of the exact, one-sided 90% CI is 35.4%).

    Measured: Up to 1 year

Timeline

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

  1. First posted19 Apr 2017
  2. Study start24 Apr 2017
  3. Primary completionNov 2026 (estimated)
  4. Study completionNov 2026 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03121014
Sponsor's protocol ID
2017-0001
Status last verified
Oct 2026
First submitted
14 Apr 2017
Last updated
13 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Maahs L, Avila AM, Koshy M, Sweiss K, Ahn KH, Chen Z, Uzoka C, Galvez C, Sanchez M, Rubinstein P, Quigley J, Zucchetti E, Mahmud N, Aydogan B, Patel P, Rondelli D. Intensified conditioning with high-dose total marrow irradiation and myeloablative chemotherapy reduces risk of relapse without increasing toxicity in allogeneic hematopoietic stem cell transplant for high-risk myeloid malignancies: a phase II study. Haematologica. 2026 Jan 1;111(1):177-183. doi: 10.3324/haematol.2025.287457. Epub 2025 Jun 19.

    PubMed 40534485

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludarabine, Busulfan and ATG in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by University of Illinois Chicago 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 18 inclusion and 23 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: under way, not looking for participants, as of the sponsor's last update on 13 Oct 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?

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 of approximately 30% in high-risk patients conditioned with the Fludarabine/ Busulfan regimen (time frame: Up to 1 year). 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 NCT03121014, which also lists 1 linked publication.

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 13 Oct 2026.

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

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in