Total Marrow and Lymphoid Irradiation in Combination With Fludarabine and Melphalan as Conditioning for Allogeneic Peripheral Blood Stem Cell Hematopoietic Cell Transplant in Older Patients With Refractory and Relapsed Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 50 years (no upper age limit)
• Note: Patients ≥ 18 years and < 50 years are also included if they are not candidates for myeloablative conditioning regimens due to comorbidities or active disease
• Karnofsky or Lansky performance status ≥ 70
• Eligible patients will have a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories:
• Acute myeloid leukemia (AML):
• Patients with de novo or secondary disease in unfavorable risk group including poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for AML i.e., monosomal karyotype, -5,5q-,-7,7q-,11q23-non t(9;11), inv (3), t(3;3), t(6;9), t(9;22) and complex karyotypes (≥ 3 unrelated abnormalities), or all patient in intermediate risk groups
• Patients with active disease:
• Morphologically
• Minimal residual disease (MRD) testing (MRD+ through flow cytometry, cytogenetics, or molecular assays)
• Myelodysplastic syndrome/chronic myelomonocytic leukemia (CMML) (MDS) with ≥ 10% blast
• Patients must have an human leukocyte antigen (HLA) (A, B, C, and DRB1) identical sibling or a 8/8 (A, B, C, and DR) allele matched unrelated donor who is willing to donate primed blood stem cells
• Serum direct bilirubin ≤ 2.0 x upper limit of normal (ULN) (unless has Gilbert's disease) (within 35 days prior to day 1 of protocol therapy unless otherwise stated)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN (within 35 days prior to day 1 of protocol therapy unless otherwise stated)
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN (within 35 days prior to day 1 of protocol therapy unless otherwise stated)
• Creatinine clearance of ≥ 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 35 days prior to day 1 of protocol therapy unless otherwise stated)
• Left ventricular ejection fraction (LVEF) ≥ 50%
• Note: To be performed within 35 days prior to day 1 of protocol therapy
• If able to perform pulmonary function tests: Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and DLCO (diffusion capacity) ≥ 50% of predicted (corrected for hemoglobin)
• Note: To be performed within 35 days prior to day 1 of protocol therapy
• If unable to perform pulmonary function tests: Oxygen (O2) saturation > 92% on room air
• Note: To be performed within 35 days prior to day 1 of protocol therapy
• Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) (within 35 days prior to day 1 of protocol therapy unless otherwise stated)
• If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Meets institutional and federal requirements for infectious disease titer requirements
• Note: Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
• Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test (within 35 days prior to day 1 of protocol therapy unless otherwise stated)
• If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
• Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

You cannot join if

• Allogeneic stem cell transplant or autologous HCT within 1 year prior to day 1 of protocol therapy
• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 days of day 1 of protocol therapy
• Note: Low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted. These include hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors (TKIs). TKIs can also be given up to 3-5 days before conditioning regimen
• More than three previous lines of intensive chemotherapy, where the regimen intent was to induce remission
• Co-enrollment in other clinical trials involving post-HCT maintenance interventions or any study with potential to affect disease-free survival is not allowed
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Clinically significant uncontrolled illness
• Active infection not responding to antibiotics
• Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

Treatments listed in the registry

• Biospecimen Collection (Procedure): Undergo urine and blood sample collection
• Bone Marrow Biopsy (Procedure): Undergo bone marrow biopsy
• Computed Tomography (Procedure): Undergo CT
• Echocardiography Test (Procedure): Undergo echocardiography
• Fludarabine Phosphate (Drug): Given IV
• Melphalan (Drug): Given IV
• Multigated Acquisition Scan (Procedure): Undergo MUGA
• Palifermin (Biological): Given IV
• Peripheral Blood Stem Cell Transplantation (Procedure): Undergo allogeneic PBSC HCT
• Questionnaire Administration (Other): Ancillary studies
• Sirolimus (Drug): Given sirolimus
• Tacrolimus (Drug): Given IV or PO
• Total Marrow and Lymphoid Irradiation (Radiation): Undergo TMLI

Na · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• biopsy: Part of the study plan
• bone marrow: Part of the study plan
• blood samples: Part of the study plan
• CT scans: Part of the study plan
• echocardiogram: Part of the study plan
• questionnaires: Part of the study plan

Main goals

• Leukemia-free survival (From the date of stem cell infusion to the date of first observation of relapse/progression, or date of death, whichever comes first, assessed at 2 years post-hematopoietic cell transplantation (HCT))

Other goals

• Incidence of adverse events (AEs)
• Incidence of highest grades of AEs
• Overall survival
• Relapse
• Non-relapse mortality
• Acute graft-versus-host disease (GVHD)
• Chronic GVHD
• GVHD-free and relapse-free survival

Planned enrollment: 35 (estimated).

• City of Hope Medical Center, Duarte, California

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07582172

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 7, 2026. Public record; not medical advice.