TMLI Plus Chemotherapy in High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

NCT06598969 | Not Yet Recruiting Phase 2

• 1 other identifier: TMLI-MA
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Single-arm, single-center phase II trial to evaluate the antileukemic activity and safety/tolerability of TMLI/cyclophosphamide and etoposide conditioning regimen followed by allogeneic hematopoietic stem cell transplantation in patients with high-risk myelodysplastic syndrome or acute myeloid leukemia.

Conditions

Myelodysplastic Syndromes; Myeloid Leukemia, Acute

Keywords

High-Risk myelodysplastic syndrome; Acute myeloid leukemia; Total narrow and lymphoid irradiation

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Time from the start of treatment to the date of death, disease relapse/progression, or date of last follow-up.

  From the start of therapy to 2 years after post-transplant

Secondary Outcomes (9)

• Overall survival

  From the start of therapy to 2 years after post-transplant

• Cumulative incidence of recurrence/progression

  From the start of therapy to 2 years after post-transplant

• Complete remission rate

  From the day of infusion to the day 30 post-transplant

• Non-relapse mortality

  From the start of therapy until 2 years after post-transplant

• Measurable residual disease

  At 30, 90, 180 days and 1 year, 1.5 year and 2 years post-transplant

Study Arms (1)

Single arm

EXPERIMENTAL

This trial is designed to evaluate the antileukemic activity of an Total bone marrow and lymphoid irradiation/cyclophosphamide/etoposide conditioning regimen for allogeneic hematopoietic stem cell transplantation, in patients with high-risk myelodysplastic syndromes and acute myeloid leukemia, as assessed by 2-year progression-free survival. The first 6-18 patients enrolled/treated in this study will be part of a safety sub-analysis, so patients will be assigned to the dose level that is currently open once they are verified to be eligible; up to three dose levels can be studied.

Drug: Total bone marrow and lymphoid irradiation/cyclophosphamide/etoposide

Interventions

Total bone marrow and lymphoid irradiation/cyclophosphamide/etoposide DRUG

Evaluate the antileukemic activity of an total bone marrow and lymphoid irradiation/cyclophosphamide/etoposide conditioning regimen for allogeneic hematopoietic stem cell transplantation

Single arm

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• The participant has the ability and willingness to sign the informed consent document
• Age ≥18 to ≤50 years.
• Karnofsky's performance status should be ≥70%.
• Patients with myelodysplastic syndrome/acute myeloid leukemia or acute myeloid leukemia with relapsed/refractory active disease, or in complete remission or morphologic leukemia-free state with evidence of measurable residual disease as assessed by multiparameter flow cytometry (≥ 0,1%) or next-generation sequencing
• All candidates for this study must have an Human leukocyte antigens (A, B, C, DR) identical siblings who are willing to donate bone marrow or peripheral blood hematopoietic progenitors or an 8/8 matched unrelated donor. A single allele mismatch in A, B, C or DR beta chain 1 shall be allowed
• Total bilirubin ≤ 1.5 x upper limit of normal or 3 x upper limit of normal for Gilbert's disease.
• serum glutamate oxaloacetate transaminase \& serum glutamate pyruvate transaminaseT ≤ 5 x upper limit of normal.
• Serum creatinine ≤ 1.3 mg/dL or creatinine clearance measured ≥ 80 mL/min for 24 hours of urine collection
• Women of childbearing age only: Negative urine or serum pregnancy test
• Pulmonary function tests: forced expiratory volume in one second and Carbon Monoxide Diffusion Capacity (adjusted for Hb) ≥ 50% from expected normal value
• Patients should undergo cardiac evaluation with an electrocardiogram showing no ischemic changes or clinically relevant arrhythmia, and a ≥50% ejection fraction established by Multi-Gated Acquisition Scan or echocardiogram
• Men and women of childbearing potential agree to use appropriate contraceptives (hormonal or barrier contraception or abstinence) prior to study entry and for six months following the duration of study participation
• The time elapsed since the end of the last induction or reinduction cycle must be greater than or equal to 14 days

You may not qualify if:

• Patients who have received a previous autologous (within the last year) or allogeneic transplant (at any time) are excluded
• Previous radiation therapy, which would preclude the use of total bone marrow and lymphoid irradiation
• Plans during the trial to receive any other investigational (non-trial-related) agents
• Uncontrolled disease, including ongoing or active infection
• History of allergic reactions attributed to compounds of chemical or biological composition similar to cyclophosphamide or etoposide
• Patients with other active malignancies are not eligible for this study, other than the malignancies discussed
• Patients with a psychological or medical condition that the patient's physician deems unacceptable to proceed with allogeneic hematopoietic stem cell transplantation
• Women who plan to become pregnant or breastfeed during the trial
• Patients who do not agree to practice effective forms of contraception
• Subjects who, in the opinion of the investigator, may not be able to meet the safety control requirements of the study

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead

Study Sites (1)

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Lymphatic Irradiation

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics

Study Officials

• José Antonio Pérez Simón, MD-PhD

  Fundación para la Gestión de la Investigación en Salud de Sevilla

  PRINCIPAL INVESTIGATOR

Central Study Contacts

José Antonio Pérez Simón, MD-PhD

CONTACT

+34955013260; josea.perez.simon.sspa@juntadeandalucia.es

Clara M Rosso Fernández, MD-PhD

CONTACT

+34955013414; claram.rosso.sspa@juntadeandalucia.es

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: To evaluate the antileukemic activity and safety/tolerability of the TMLI/cyclophosphamide and etoposide conditioning regimen followed by allogeneic hematopoietic stem cell transplantation in patients with high-risk myelodysplastic syndrome or acute myeloid leukemia

Study Record Dates

• First Submitted: August 28, 2024
• First Posted: September 19, 2024
• Study Start: December 30, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)