NCT06602323

TMLI/Fludarabine/Melphalan Conditioning for Allogeneic Transplantation in High-risk Myelodysplastic Syndrome or Acute Myeloid Leukemia.

Phase II Study of Total Marrow and Lymphoid Irradiation (TMLI) Administered in Combination With a Reduced-intensity Regimen Based on Fludarabine and Melphalan as Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT) in Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia.

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla · Academic / Other
• Sex: All
• Age: 50 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn if drugs (fludarabine and melphalan) combinated with a targeted irradiation (in bone marrow and in lymphoid tissue) works to treat blood cancers (high risk myelodysplastic syndrome or acute myeloid leukemia) in adults. It will also learn about the safety of this combination of drugs and irradiation. The main questions it aims to answer are: * Does this combined therapy result in an improved survival and decreased relapse/progression rate after a bone marrow transplant? * What toxicities or complications do participants have when taking this combined therapy? Researchers will use this combined therapy to see if it works to treat high risk myelodysplastic syndrome or acute myeloid leukemia through the evaluation of the length of time (during the treatment and 2 years after the treatment) that a patient lives with the disease but it does not get worse (progression-free survival). Participants will: * Receive the combined therapy (study treatment) one week before the bone marrow transplant. * Receive too post-transplant medication as per usual clinical practice. Patients will have to attend medical visits (checkups and tests) for 2 years.

Detailed description

This is a single-arm, single center phase II trial to evaluate the antileukemic activity and safety of the AHSCT TMLI/Flu/Mel conditioning regimen in patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. A patient safety-lead phase will be carried out to ensure there are no unexpected toxicities. Ultimately, a total of 34 patients will be treated at the TMLI/Flu/Mel dose level deemed safe as determined during the introductory patient safety segment of this study. Up to three dose levels can be studied. A 3+3 de-escalation design comprising a patient safety-lead phase will be applied in successive patient cohorts to evaluate the safety of the TMLI schedule and identify the optimal treatment dose: Initially, 3 patients will be treated at the starting TMLI dose (Dose Level 1, 1200 cGy). If 0 or 1 DLT is observed among the first 6 patients at Dose Level 1, then 28 additional patients will be treated at this dose level (allowing for the evaluation of 34 patients treated at the target dose level). If ≥2/6 patients experience a DLT at Dose Level 1, then the MTD has been exceeded and the next lower TMLI dose (Dose Level -1, 1100 cGy) will be expanded to up to 6 patients. If 0 or 1 patient out of 6 experiences a DLT, this dose level will be further evaluated (n=28 additional patients). If ≥2/6 patients experience a DLT, the next lower dose (Dose Level -2, 1000 cGy) level will be expanded applying the same criteria. No further dose level reductions will be allowed beyond Dose Level -2. No more than 3 patients may be \<30 days after stem cell infusion at any time during patient safety introduction. The tacrolimus dose and MMF dose will remain fixed for all defined dose levels and will not be reduced at any time. Considering this proposed design, the expected sample size of the study will be n=34 patients, with a potential minimum and maximum size of n=34 and n=46, respectively.

Conditions

• Myelodysplastic Syndromes
• Acute Myeloid Leukemia

Interventions

Type	Name	Description
COMBINATION_PRODUCT	TMLI/Flu/Mel	Targeted total bone marrow and lymphoid irradiation (TMLI) conformal therapy administered in combination with a reduced-intensity regimen based on Fludarabine and Melphalan.

Timeline

• Start date: 2024-10-01
• Primary completion: 2028-10-01
• Completion: 2028-10-01
• First posted: 2024-09-19
• Last updated: 2024-09-19