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

Starting soon · Phase 2

Conditions studied: Acute Myeloid Leukemia With Complex Karyotype, Myelodysplastic Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Recurrent Myelodysplastic Chronic Myelomonocytic Leukemia, Recurrent Myelodysplastic Syndrome, Recurrent Secondary Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Refractory Myelodysplastic Chronic Myelomonocytic Leukemia, Refractory Myelodysplastic Syndrome, Refractory Secondary Acute Myeloid Leukemia

In brief

This phase II trial tests the effect of total marrow and lymphoid irradiation (TMLI) in combination with fludarabine and melphalan as conditioning regimen in older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that has not responded to previous treatment (refractory) and that has come back after a period of improvement (relapsed) and are undergoing a donor (allogeneic) peripheral blood stem cell (PBSC) hematopoietic cell transplant (HCT) from a matched related or unrelated donor. HCT is the only curative treatment for high-risk patients, but the side effects related to the current conditioning treatments limit the use to younger and more fit patients. TMLI is a targeted form of total body radiation that uses intensity-modulated radiation therapy to target marrow, lymph node chains, and the spleen. It is designed to reduce radiation-associated side effects and maximize the radiation therapeutic effect. Fludarabine blocks cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. It is a type of purine antagonist and a type of ribonucleotide reductase inhibitor. Melphalan is in a class of medications called alkylating agents. It may kill cancer cells by damaging their DNA and stopping them from dividing. Giving chemotherapy, such as fludarabine and melphalan, and TMLI before an allogeneic 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 healthy stem cells from a related or unrelated donor, such as PBSC HCT, that closely match the patient's blood, are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets, an may help destroy any remaining cancer cells. Giving TMLI in combination with fludarabine and melphalan as conditioning treatment for an allogeneic PBSC HCT from a matched related or unrelated donor may be safe, tolerable, and/or effective in treating high-risk older patients with relapsed and refractory acute myeloid leukemia or high-risk myelodysplastic syndrome.

Key facts

Study ID

NCT07582172

Run by

City of Hope Medical Center

People needed

35

Starts

2027-04-05

Expected to finish

2029-04-05

Last updated by the study team

2026-05-12

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify 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

You may not qualify 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)

Where it is running

• City of Hope Medical Center — Duarte, California, United States

Full record on ClinicalTrials.gov

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