Acute Myeloid LeukemiaPhase 2NCT07634536
Automated Total Marrow and Lymphoid Irradiation for Allogeneic Hematopoietic Cell Transplant
A Phase 2 study testing VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI), Fludarabine and Cyclophosphamide in people with Acute Myeloid Leukemia and Myeloproliferative Neoplasm, run by Stanford University at 1 site in United States.
Trial summary
Intensive conditioning regimens used in allogeneic hematopoietic cell transplant (HCT) help to eliminate hematologic tumors and reduce the risk of relapse, but are also characterized by high toxicity. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Myeloid Leukemia, Myeloproliferative Neoplasm, Myelodysplastic Syndromes
- What is being tested?
- VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI), Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2026to Aug 2028
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age, Performance Status, and Graft Criteria require all of the following bullet points:
- Age 18 to 60 years (inclusive)
- HCT Co-Morbidity score (HCT-CI) < 5 (http://www.qxmd.com/calculate-online/hematology/hct-ci)(31)
- Adequate performance status is defined as Karnofsky score ≥ 70%
- Patients must be receiving an allogeneic peripheral blood stem cell graft
- Patients and selected donor must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1. Donors may be an 8/8 matched sibling donor, 8/8 matched unrelated donor, haploidentical related donor, or 7/8 mismatched unrelated donor.
Show all 30Show fewer
- Eligible Diseases (Any one of the following)
- Acute Myeloid Leukemia (AML) Must have at least one of the following characteristics:
- Blasts >5% in the peripheral blood and/or bone marrow after >2 prior lines of AML directed therapy, present during the trial screening window
- Adverse plus risk by AlloHCT Refined ELN Criteria: defined as having complex cytogenetics, TP53 mutation, or MECOM rearrangement confirmed at any time point.(32)
- Myelodysplastic syndrome Must have at least one of the following characteristics at the time of conditioning:
- Blasts >10% in the peripheral blood and/or bone marrow after >1 prior line of therapy.
- TP53 mutation confirmed at any time point
- Myeloproliferative neoplasms (MPN) or MDS/MPN overlap. Must have at least one of the following characteristics:
- Blasts >10% in the peripheral blood and/or bone marrow during the trial screening window
- TP53 mutation confirmed at any time point
- Adequate organ function is defined as all of the following:
- Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 45% confirmed by MUGA or echocardiography Pulmonary: DLCO, FEV1, FVC > 50% predicted, and absence of O2 requirements. Liver: Transaminases < 3 x upper limit of normal (ULN) and total bilirubin ≤ 2 mg/dL except for patients with Gilbert's syndrome or hemolysis (as indicated by provider documentation).
- Renal: Creatinine < 2.0 mg/dL (adults) and creatinine clearance > 40 mL/min.
- Must be FIRST allogeneic HCT
- Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment.
- Voluntary written consent
- Age, Performance Status, and Graft Criteria require all of the following bullet points:
- Age 18 to 70 years (inclusive) Adequate performance status is defined as Karnofsky score ≥ 70% Patients must be receiving an allogeneic peripheral blood stem cell graft Patients and selected donor must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1. Donors may be an 8/8 matched sibling donor, 8/8 matched unrelated donor, haploidentical related donor, or 7/8 mismatched unrelated donor.
- Eligible Diseases (Any of the following) Acute Myeloid Leukemia (AML) Myelodysplastic syndrome Myeloproliferative neoplasm MDS/MPN overlap
- Must have relapse after prior allo HCT
- Adequate organ function is defined as all of the following:
- Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 40% confirmed by MUGA or echocardiography Pulmonary: DLCO, FEV1, FVC > 40% predicted, and absence of O2 requirements. Liver: Transaminases < 3 x upper limit of normal (ULN) and total bilirubin ≤ 2 mg/dL except for patients with Gilbert's syndrome or hemolysis (as indicated by provider documentation).
- Renal: Creatinine < 2.0 mg/dL (adults) and creatinine clearance > 40 mL/min. Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment.
- Voluntary written consent
Who cannot join
- Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
- Untreated active infection. Controlled or asymptomatic infections requiring continued antimicrobial therapy are permissible.
- Active HIV infection, defined as HIV infection with detectable viral load
- Active central nervous system malignancy
- GVHD requiring systemic therapy including > 0.25 mg/kg prednisone (or equivalent) or other systemic therapy for GVHD (e.g., tacrolimus, sirolimus, ruxolitinib, belumosodil, ibrutinib, axatilimab).
- Any other medical or psychological condition that is deemed serious and unsafe for clinical trial participation.
- Exposure to prior radiation that is deemed unsafe for clinical trial participation.
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
Stanford University
Palo Alto, California, 94304
Hany Elmariah, MD, 650-723-0822, he3@stanford.edu
Hany Elmariah, MD
About this study
Intensive conditioning regimens used in allogeneic hematopoietic cell transplant (HCT) help to eliminate hematologic tumors and reduce the risk of relapse, but are also characterized by high toxicity. Total marrow and lymphoid irradiation (TMLI) is a specialized radiation technique that specifically targets marrow and lymphoid tissue to maximize antitumor efficacy while reducing off target toxicity. Despite these benefits, TMLI is technically challenging and time consuming. The radiation oncology team at Stanford has developed an automated TMLI platform to overcome these challenges. In this phase II trial, automation will be incorporated into a previously validated conditioning regimen of fludarabine/cyclophosphamide/TMLI HCT with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis to confirm the feasibility and safety of automation in patients receiving allogeneic HCT for high-risk myeloid malignancies.
- Being tested
- VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI), Fludarabine, Cyclophosphamide, Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT), Mycophenolate mofetil (MMF)
- Medical subject headings
- Leukemia, Myeloid, Acute, Myeloproliferative Disorders, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI)Radiation
Patients receive VMAT-based TMLI with daily image-guided radiation therapy (IGRT) for treatment localization and verification prior to radiation delivery.
FludarabineDrug
Fludarabine 25 mg/m² IV administered daily on Days -7 through -3.
CyclophosphamideDrug
Cyclophosphamide 14.5 mg/kg IV on Days -7 and -6 as part of conditioning and 50 mg/kg IV on Days +3 and +4 as post-transplant GVHD prophylaxis.
Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT)Biological
Allogeneic peripheral blood stem cell transplantation administered on Day 0.
Mycophenolate mofetil (MMF)Drug
Mycophenolate mofetil initiated on Day +5 and continued through Day +35 for GVHD prophylaxis.
TacrolimusDrug
Mycophenolate mofetil initiated on Day +5 and continued through Day +35 for GVHD prophylaxis.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning Regimen | Experimental | Participants receive fludarabine, cyclophosphamide, and TMLI 200 cGy BID conditioning followed by allogeneic peripheral blood stem cell transplantation (PBSCT). Post-transplant GVHD prophylaxis includes cyclophosphamide, mycophenolate mofetil, and tacrolimus. Receives: Radiation: VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI); Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT); Drug: Mycophenolate mofetil (MMF); Drug: Tacrolimus |
| Cohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen | Experimental | Participants receive fludarabine, cyclophosphamide, and TMLI 150 cGy BID conditioning followed by allogeneic peripheral blood stem cell transplantation (PBSCT). Post-transplant GVHD prophylaxis includes cyclophosphamide, mycophenolate mofetil, and tacrolimus. Receives: Radiation: VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI); Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT); Drug: Mycophenolate mofetil (MMF); Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-Relapse Mortality (NRM)
Death without prior disease relapse following allogeneic peripheral blood stem cell transplantation.
Measured: Day 100 after transplantation
Neutrophil Engraftment
Neutrophil engraftment following allogeneic peripheral blood stem cell transplantation.
Measured: Through Day 100 after transplantation
Secondary outcomes (6)
Risk of Relapse
Disease relapse following allogeneic peripheral blood stem cell transplantation.
Measured: Day 100 post-transplant
Disease-Free Survival (DFS)
Disease-free survival following allogeneic peripheral blood stem cell transplantation.
Measured: Day 100 post-transplant
Overall Survival (OS)
Overall survival following allogeneic peripheral blood stem cell transplantation.
Measured: Day 100 post-transplant
Incidence of Grade II-IV Acute Graft-versus-Host Disease (GVHD)
Incidence and severity of Grade II-IV acute graft-versus-host disease following allogeneic peripheral blood stem cell transplantation.
Measured: Day 100 post-transplant
Incidence of Grade III-IV Acute Graft-versus-Host Disease (GVHD)
Incidence and severity of Grade III-IV acute graft-versus-host disease following allogeneic peripheral blood stem cell transplantation.
Measured: Day 100 post-transplant
Bearman Regimen-Related Toxicity
Regimen-related toxicity assessed using the Bearman Toxicity Scale. Toxicity will be evaluated by organ system and graded according to severity (Grades I-IV).
Measured: Day 100 post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2026
- Study startNov 2026 (estimated)
- Primary completionAug 2028 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hany Elmariah, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07634536
- Sponsor's protocol ID
- IRB-86777
- Status last verified
- Sep 2026
- First submitted
- 4 Jun 2026
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Automated Total Marrow and Lymphoid Irradiation for Allogeneic Hematopoietic Cell Transplant
- ClinicalTrials.gov ID
- NCT07634536
- Acronym / sponsor ID
- IRB-86777
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Nov 2026 (estimated)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 9 Jun 2026 (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.
Intensive conditioning regimens used in allogeneic hematopoietic cell transplant (HCT) help to eliminate hematologic tumors and reduce the risk of relapse, but are also characterized by high toxicity. Total marrow and lymphoid irradiation (TMLI) is a specialized radiation technique that specifically targets marrow and lymphoid tissue to maximize antitumor efficacy while reducing off target toxicity. Despite these benefits, TMLI is technically challenging and time consuming. The radiation oncology team at Stanford has developed an automated TMLI platform to overcome these challenges. In this phase II trial, automation will be incorporated into a previously validated conditioning regimen of fludarabine/cyclophosphamide/TMLI HCT with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis to confirm the feasibility and safety of automation in patients receiving allogeneic HCT for high-risk myeloid malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning Regimen | Experimental | Radiation: VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI), Drug: Fludarabine, Drug: Cyclophosphamide, Biological: Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT), Drug: Mycophenolate mofetil (MMF), Drug: TacrolimusParticipants receive fludarabine, cyclophosphamide, and TMLI 200 cGy BID conditioning followed by allogeneic peripheral blood stem cell transplantation (PBSCT). Post-transplant GVHD prophylaxis includes cyclophosphamide, mycophenolate mofetil, and tacrolimus. |
| Cohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen | Experimental | Radiation: VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI), Drug: Fludarabine, Drug: Cyclophosphamide, Biological: Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT), Drug: Mycophenolate mofetil (MMF), Drug: TacrolimusParticipants receive fludarabine, cyclophosphamide, and TMLI 150 cGy BID conditioning followed by allogeneic peripheral blood stem cell transplantation (PBSCT). Post-transplant GVHD prophylaxis includes cyclophosphamide, mycophenolate mofetil, and tacrolimus. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Age, Performance Status, and Graft Criteria require all of the following bullet points:
- Eligible Diseases (Any one of the following)
- Myelodysplastic syndrome Must have at least one of the following characteristics at the time of conditioning:
- Myeloproliferative neoplasms (MPN) or MDS/MPN overlap. Must have at least one of the following characteristics:
- Adequate organ function is defined as all of the following:
Key exclusion criteria (7 listed)
- Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
- Untreated active infection. Controlled or asymptomatic infections requiring continued antimicrobial therapy are permissible.
- Active HIV infection, defined as HIV infection with detectable viral load
- Active central nervous system malignancy
- GVHD requiring systemic therapy including > 0.25 mg/kg prednisone (or equivalent) or other systemic therapy for GVHD (e.g., tacrolimus, sirolimus, ruxolitinib, belumosodil, ibrutinib, axatilimab).
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 |
|---|---|---|
| VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI)Patients receive VMAT-based TMLI with daily image-guided radiation therapy (IGRT) for treatment localization and verification prior to radiation delivery. | Radiation | Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning Regimen, Cohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen |
| FludarabineFludarabine 25 mg/m² IV administered daily on Days -7 through -3. | Drug | Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning Regimen, Cohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen |
| CyclophosphamideCyclophosphamide 14.5 mg/kg IV on Days -7 and -6 as part of conditioning and 50 mg/kg IV on Days +3 and +4 as post-transplant GVHD prophylaxis. | Drug | Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning Regimen, Cohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen |
| Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT)Allogeneic peripheral blood stem cell transplantation administered on Day 0. | Biological | Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning Regimen, Cohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen |
| Mycophenolate mofetil (MMF)Mycophenolate mofetil initiated on Day +5 and continued through Day +35 for GVHD prophylaxis. | Drug | Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning Regimen, Cohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen |
| TacrolimusMycophenolate mofetil initiated on Day +5 and continued through Day +35 for GVHD prophylaxis. | Drug | Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning Regimen, Cohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen |
Primary outcome
Non-Relapse Mortality (NRM)
Time frame: Day 100 after transplantation
Death without prior disease relapse following allogeneic peripheral blood stem cell transplantation.
Neutrophil Engraftment
Time frame: Through Day 100 after transplantation
Neutrophil engraftment following allogeneic peripheral blood stem cell transplantation.
6 secondary outcomes
Risk of Relapse
Time frame: Day 100 post-transplant
Disease-Free Survival (DFS)
Time frame: Day 100 post-transplant
Overall Survival (OS)
Time frame: Day 100 post-transplant
Incidence of Grade II-IV Acute Graft-versus-Host Disease (GVHD)
Time frame: Day 100 post-transplant
Incidence of Grade III-IV Acute Graft-versus-Host Disease (GVHD)
Time frame: Day 100 post-transplant
Bearman Regimen-Related Toxicity
Time frame: Day 100 post-transplant
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 30 Sep 2026.
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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.
Hany Elmariah, MD principal investigator
Stanford University
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 VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI), Fludarabine and Cyclophosphamide in people with Acute Myeloid Leukemia and Myeloproliferative Neoplasm, run by Stanford University 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 30 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: opening soon, as of the sponsor's last update on 30 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 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 Hany Elmariah (650-723-0822, he3@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Non-Relapse Mortality (NRM) (time frame: Day 100 after transplantation). 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?
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 30 Sep 2026.