Myelodysplastic SyndromesPhase 2TMLI-MANCT06598969
TMLI Plus Chemotherapy in High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia
A Phase 2 study testing Total bone marrow and lymphoid irradiation/cyclophosphamide/etoposide in people with Myelodysplastic Syndromes and Myeloid Leukemia, Acute, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Myelodysplastic Syndromes, Myeloid Leukemia, Acute
- What is being tested?
- Total bone marrow and lymphoid irradiation/cyclophosphamide/etoposide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteSpain
- Study dates
- 30 Dec 2024to 30 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site
Hospital Universitario Virgen del Rocío
Seville, 41013
Jose-Antonio Perez-Simon, 0034955013260 ext. 0034, josea.perez.simon.sspa@juntadeandalucia.es
About this study
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
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.
Read the 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.
- Conditions
- Myelodysplastic Syndromes, Myeloid Leukemia, Acute
- Being tested
- Total bone marrow and lymphoid irradiation/cyclophosphamide/etoposide
- Keywords
- High-Risk myelodysplastic syndrome, Acute myeloid leukemia, Total narrow and lymphoid irradiation
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total bone marrow and lymphoid irradiation/cyclophosphamide/etoposideDrug
Evaluate the antileukemic activity of an total bone marrow and lymphoid irradiation/cyclophosphamide/etoposide conditioning regimen for allogeneic hematopoietic stem cell transplantation
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Total bone marrow and lymphoid irradiation/cyclophosphamide/etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Time from the start of treatment to the date of death, disease relapse/progression, or date of last follow-up.
Measured: From the start of therapy to 2 years after post-transplant
Secondary outcomes (9)
Overall survival
Quantification of time of patients who are still alive
Measured: From the start of therapy to 2 years after post-transplant
Cumulative incidence of recurrence/progression
The event is relapse/progression either extramedullary or at bone marrow
Measured: From the start of therapy to 2 years after post-transplant
Complete remission rate
The event is whether or not the patient has a documented complete remission
Measured: From the day of infusion to the day 30 post-transplant
Non-relapse mortality
Number of deaths from causes other than relapse or progression
Measured: From the start of therapy until 2 years after post-transplant
Measurable residual disease
Measurable residual disease monitoring assessed by multiparameter flow cytometry
Measured: At 30, 90, 180 days and 1 year, 1.5 year and 2 years post-transplant
Incidence of infection
Describe the infections.
Measured: 2 years after post-transplant
Adverse Events
Describe the adverse event
Measured: 2 years after post-transplant
Acute graft-versus-host disease grades 2-4 and 3-4
This point is classified according to the consensus MAGIC classification
Measured: 100 days post-transplant
Chronic graft-versus-host disease
Describe the chronic graft-versus-host disease according to the National Institutes of Health Stroke Scale consensus staging.
Measured: 2 years after post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start30 Dec 2024 (estimated)
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- 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
- Masking
- None (open label)
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- José Antonio Pérez Simón, MD-PhD, Principal investigator, Fundación para la Gestión de la Investigación en Salud de Sevilla
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06598969
- Sponsor's protocol ID
- TMLI-MA
- Acronym
- TMLI-MA
- Status last verified
- Sep 2024
- First submitted
- 28 Aug 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06598969
- Acronym / sponsor ID
- TMLI-MA / TMLI-MA
- Conditions
- Myelodysplastic Syndromes, Myeloid Leukemia, Acute
- Keywords
- High-Risk myelodysplastic syndrome, Acute myeloid leukemia, Total narrow and lymphoid irradiation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Study start
- 30 Dec 2024 (estimated)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: Total bone marrow and lymphoid irradiation/cyclophosphamide/etoposideThis 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Total bone marrow and lymphoid irradiation/cyclophosphamide/etoposideEvaluate the antileukemic activity of an total bone marrow and lymphoid irradiation/cyclophosphamide/etoposide conditioning regimen for allogeneic hematopoietic stem cell transplantation | Drug | Single arm |
Primary outcome
Progression-free survival
Time frame: From the start of therapy to 2 years after post-transplant
Time from the start of treatment to the date of death, disease relapse/progression, or date of last follow-up.
9 secondary outcomes
Overall survival
Time frame: From the start of therapy to 2 years after post-transplant
Cumulative incidence of recurrence/progression
Time frame: From the start of therapy to 2 years after post-transplant
Complete remission rate
Time frame: From the day of infusion to the day 30 post-transplant
Non-relapse mortality
Time frame: From the start of therapy until 2 years after post-transplant
Measurable residual disease
Time frame: At 30, 90, 180 days and 1 year, 1.5 year and 2 years post-transplant
Incidence of infection
Time frame: 2 years after post-transplant
Adverse Events
Time frame: 2 years after post-transplant
Acute graft-versus-host disease grades 2-4 and 3-4
Time frame: 100 days post-transplant
Chronic graft-versus-host disease
Time frame: 2 years after post-transplant
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
José Antonio Pérez Simón, MD-PhD principal investigator
Fundación para la Gestión de la Investigación en Salud de Sevilla
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Total bone marrow and lymphoid irradiation/cyclophosphamide/etoposide in people with Myelodysplastic Syndromes and Myeloid Leukemia, Acute, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact José Antonio Pérez Simón, MD-PhD (+34955013260, josea.perez.simon.sspa@juntadeandalucia.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: From the start of therapy to 2 years after post-transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.