Preparation for bone marrow transplant through the combined use of chemo and radiotherapy (intensive or myeloablative: eliminates stem cells)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Feb 2025 → ongoing

Decision date (initial)

2024-11-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ISCIII institute public funding

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The antitumor activity of the conditioning regimen with TMLI, cyclophosphamide and etoposide followed by AHSCT will be evaluated by means of the progression-free survival (PFS) at 2 years after a safety-lead phase.

Secondary objectives 4

1. To determine the complete remission (CR) rate at day 30 post-transplant
2. To estimate overall survival (OS), cumulative incidence (CI) of recurrence/progression, and non-relapse mortality (NRM) at 100 days, 1 year, and 2 years
3. MRD monitoring at 30, 90, 180, 270, 360, 575 days and 720 days post-transplant
4. To assess early and late toxicities/complications by organ and severity, as well as dose/dose-volume toxicity characterization across organs, including acute/chronic GVHD, infection, and long-term complications

Conditions and MedDRA coding

High-Risk Myelodisplastic Syndrome or Acute Myeloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. The participant has the ability and willingness to sign the informed consent document
2. Age ≥18 to ≤50 years
3. Karnofsky’s performance status should be ≥70%
4. 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 (in the case of FLT3-ITD-mutated AML)
5. All candidates for this study must have an HLA (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 DRB1 shall be allowed
6. Total bilirubin ≤ 1.5 x ULN OR 3 x ULN for Gilbert's disease
7. SGOT & SGPT ≤ 5 x LSN
8. Serum creatinine ≤ 1.3 mg/dL or creatinine clearance measured ≥ 80 mL/min for 24 hours of urine collection
9. Women of childbearing age only: Negative urine or serum pregnancy test
10. 3. Pulmonary function tests: forced expiratory volume in one second (FEV1) and Carbon Monoxide Diffusion Capacity (DLCO) (adjusted for Hb) ≥ 50% from expected normal value
11. 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 Acquisiton Scan (MUGA) or echocardiogram
12. ECG showing no ischemic changes or clinically significant arrhythmia
13. 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
14. The time elapsed since the end of the last induction or reinduction cycle must be greater than or equal to 14 days

Exclusion criteria 10

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Toxicity, which will be graded on both the Bearman Scale and the NCI CTCAE Scale v5.0
2. The evaluation of 2-year PFS. PFS will be defined as time from the start of treatment to the ate of death, disease relapse/progression, or date of last follow-up, and estimated using the Kaplan-Meier method

Secondary endpoints 9

1. Overall survival (OS): patients are considered a failure for this endpoint if they die, regardless of the cause. The time to this event is the time from the start of protocol therapy to death, or the last follow-up, whichever comes first
2. Cumulative incidence (CI) of recurrence/progression: The event is relapse/progression either extramedullary (EM) or at bone marrow (BM) (date and place). The time to this event is measured from the start of therapy. Death without relapse/progression is considered a competing risk. Surviving patients with no history of relapse/progression are censored at the time of last follow-up
3. Complete remission (CR) rate at day 30 post-transplant: The event is whether or not the patient has a documented CR on day 30
4. Non-relapse mortality (NRM2. NRM is measured from the start of therapy until non-disease-related death, or the last follow-up, whichever comes first
5. Measurable residual disease (MRD): MRD monitoring assessed by multiparameter flow cytometry at 30, 90, 180, 360, 575 days, and 2 years post-transplant
6. Incidence of infection: Microbiologically documented infections will be reported by site of illness, date of onset, severity, and resolution, if applicable. This data will be captured through the case report form and will be collected from day 0 to 100 days after transplantation
7. Toxicities/Adverse Events: The Bearman Scale (non-hematologic) and CTCAE v. 5.0 (hematologic) will be employed. Dose/dose-volume toxicity characterization across organs will be assessed
8. Acute graft-versus-host disease (GVHD) grades 2-4 and 3-4:. The endpoint will be assessed from day 0 to 100 days post-transplant
9. Chronic graft-versus-host disease (GVHD): Chronic graft-versus-host disease is graded according to the NIH consensus staging. The first day of onset of chronic GVHD will be used to calculate cumulative incidence curves

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Sponsor organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Address

Avenida De Manuel Siurot Sn

City

Sevilla

Postcode

41013

Country

Spain

Scientific contact point

Organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Contact name

Clara María Rosso Fernández

Public contact point

Organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Contact name

Clara María Rosso Fernández

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications