Clinical trial NCT06598969: TMLI Plus Chemotherapy in High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia
Official title: Phase II Study of TMLI Administered in Combination With a Myeloablative Regimen (Cyclophosphamide + Etoposide) for Allogeneic Hematopoietic Stem Cell Transplantation in Patients With High-risk Myelodysplastic Syndrome or Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Myeloid Leukemia, Acute
Keywords: High-Risk myelodysplastic syndrome
Acute myeloid leukemia
Total narrow and lymphoid irradiation
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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
Primary purpose: OTHER

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.

Detailed description: The aim of this study is the evaluation of the antitumor activity of the conditioning regimen with TMLI, cyclophosphamide and etoposide followed by allogeneic hematopoietic stem cell transplantation by means of the progression-free survival at 2 years after a safety-lead phase.

The determination of the complete remission rate at day 30 post-transplant, the estimation of overall survival, the cumulative incidence of recurrence/progression, and non-relapse mortality at 100 days, 1 year, and 2 years, the Minima Residual Disease monitoring at 30, 90, 180, 270 days and 1 year, 1 year and a half and 2 years post-transplant, and the assessment early and late toxicities/complications by organ and severity, as well as dose/dose-volume toxicity characterization across organs, including acute/chronic graft-versus-host disease, infection, and long-term complications are included as secondary objectives.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Progression-free survival
timeFrame: From the start of therapy to 2 years after post-transplant
Secondary outcomes:
measure: Overall survival
timeFrame: From the start of therapy to 2 years after post-transplant
measure: Cumulative incidence of recurrence/progression
timeFrame: From the start of therapy to 2 years after post-transplant
measure: Complete remission rate
timeFrame: From the day of infusion to the day 30 post-transplant
measure: Non-relapse mortality
timeFrame: From the start of therapy until 2 years after post-transplant
measure: Measurable residual disease
timeFrame: At 30, 90, 180 days and 1 year, 1.5 year and 2 years post-transplant
measure: Incidence of infection
timeFrame: 2 years after post-transplant
measure: Adverse Events
timeFrame: 2 years after post-transplant
measure: Acute graft-versus-host disease grades 2-4 and 3-4
timeFrame: 100 days post-transplant
measure: Chronic graft-versus-host disease
timeFrame: 2 years after post-transplant
Other outcomes:
Locations:
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
Study officials:
affiliation: Fundación para la Gestión de la Investigación en Salud de Sevilla
name: José Antonio Pérez Simón, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: