Studying Conditioning Regimen In Pediatric Transplantation -AML

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

7 Jun 2022 → ongoing

Decision date (initial)

2025-05-09

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-505512-37-00

EudraCT number

2021-003282-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To investigate if a conditioning regimen containing one alkylator (Bu) combined
with two antimetabolites (Clo and Flu) results in superior 2-year acute grade III to
IV-free, chronic non-limited GvHD-free, relapse free survival (GRFS) than a
conditioning regimen combining three alkylating agents (BuCyMel).

Secondary objectives 16

1. 1.To compare the following outcomes between the 2 arms of the trial: -neutrophil and platelet engraftment,
2. -rate of primary and secondary graft failure,
3. - cumulative incidence of disease relapse,
4. -cumulative incidence of transplant-related mortality,
5. - disease-free and overall survival
6. -incidence of grade II-IV and III-IV acute GVHD
7. -incidence of chronic GVHD,
8. - rates of Grade ≥ 3 toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0,
9. - incidence of infections,
10. - immunological recovery.
11. - quality of life,
12. - late effects,
13. - nutritional status.
14. To analyze the association between pre-HCT Minimal Residual Disease and incidence of relapse, disease-free survival, and overall survival.
15. -To estimate outcomes as above
16. -To analyze the association as above

Conditions and MedDRA coding

Acute Myeoloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Inclusion criteria for randomization part of the study -Age ≤18 years at time of initial AML, age ≤ 21 years at transplantation.
2. -no leukemic blasts in the peripheral blood (verified by flow cytometry in case immature cells are detected in the peripheral blood differential).
3. Patients must have a related or unrelated donor fulfilling any of the following criteria :
4. -HLA 10/10 allelic matched, identical, sibling BM donor
5. -HLA 10/10 or 9/10 allelic matched related/unrelated BM or PBSC donor or
6. -7.2 Inclusion criteria for observation/registration only
7. -All women of childbearing potential who have to have a negative pregnancy test within 2 weeks prior to the start of treatment.
8. - Signed informed consent.
9. - Any relapsed AML after initial treatment according to a defined international AML protocol. (NOPHO-DBH AML 2012/new protocol), OR AML in first remission with transplant indications and treatment according to national AML protocol (NOPHO-DBH AML 2012 or new protocol).
10. - In hematological remission, defined as
11. -no evidence of extramedullary disease, including in CNS
12. • < 5 % leukemic blasts confirmed by flow cytometry (in patients with an informative leukemia associated immunophenotype) in a bone marrow sample taken ≤14 days prior to start of conditioning

Exclusion criteria 15

1. Exclusion criteria for the randomization part of the study; - Diagnosis of Myelodysplastic syndrome (MDS).
2. - Diagnosis of Juvenile myelomonocytic leukemia (JMML)
3. - History of previous malignancy (AML diagnosed as secondary cancer)
4. - Known diagnosis of Fanconi anemia
5. - Prior autologous or allogeneic hematopoietic stem cell transplant.
6. - Planned prophylactic DLI or other immunotherapy interventions after HCT that are not included in the upfront protocol,
7. -Planned anti-leukemic medication after HCT that are not included in the upfront protocol
8. - Known intolerance to any of the chemotherapeutic drugs in the protocol.
9. -Major organ failure precluding administration of planned chemotherapy.
10. - Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
11. - Severe concomitant disease that does not allow treatment according to the protocol at the investigator’s discretion; e.g. malformation syndromes, cardiac malformations, metabolic disorders, renal impairment (<30% of normal glomerular filtration rate), severe pulmonary, hepatic or cardiac impairment due to toxicity or infection
12. - Karnofsky / Lansky score < 50%
13. - Females who are pregnant (positive serum or urine βHCG) or breastfeeding.
14. - Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use effective forms of birth control or abstinence for one year after transplantation
15. - Subjects unwilling or unable to comply with the study procedures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The primary endpoint is the 2-year acute grade III to IV-free, chronic non-limited GVHD-free, relapse free survival
2. GvHD III-IV, chronic non-limited GvHD, relapse, death) or last follow-up

Secondary endpoints 12

1. - Disease free Survival (DFS
2. - Overall Survival (OS)
3. - Cumulative incidence of relapse (CIR
4. - Transplant-related Mortality (TRM)
5. - Hematologic Recovery
6. - Graft Failure (GF)
7. - Immune Reconstitution
8. - Chronic GVHD
9. -Infections
10. - Toxicity
11. - Transplant-associated hormonal and gonadal late effect
12. - Nutritional status

Investigational products

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

Test 5

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Karin Mellgren

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Pediatric Clinical Research Centre

Third parties 1

Locations

6 EU/EEA countries · 12 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 57 files

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

Application history

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