Studying Conditioning Regimen In Pediatric Transplantation - AML , SCRIPT-AML

NCT ID: NCT05477589

Last Updated: 2024-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

170 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-07

Study Completion Date

2031-12-31

Brief Summary

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It is a randomized phase 3 study comparing two conditioning regimens in children with Acute Myeloid Leukemia, AML, undergoing allogenic stem cell transplantation. The primary aim is 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 than a conditioning regimen combining three alkylating agents (BuCyMel)

Detailed Description

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The study is designed as an open-label randomized phase III, multicenter superiority trial comparing two conditioning regimens CloFluBu and BuCyMel in children with acute myeloid leukemia (AML) with per-protocol indications to allogeneic hematopoietic stem cell transplantation with a myeloablative conditioning.

This study is composed of two parts - an interventional part that includes randomization, and an observational part. The interventional part is a phase III randomized, open label, multicenter parallel group trial comparing two conditioning regimens used in pediatric HCT: a three alkylator combination of busulfan, cyclophosphamide and melphalan (BuCyMel, standard arm) and a combination of clofarabine, fludarabine and busulfan in which two alkylators are replaced by antimetabolites (CloFluBu, experimental arm). The observational part will prospectively register outcome measures of transplantation in patients not fulfilling criteria for participation in the interventional part of the study (due to lack of complete remission, lack of matched sibling or unrelated donor, who were not recruited to a national upfront protocol or who decline participation in randomization) but consenting to registration of the data.

Conditions

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Acute Myeloid Leukemia (AML) in Remission Stem Cell Transplantation

Keywords

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Leukemia Leukemia, Myeloid, Acute Neoplasms Haematopoietic cell transplantation Paediatric

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

AML patient eligible for stem cells transplantation will be randomized either get conditioning regimens CloFluBu or BuCyMel.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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BuCyMel

a combination of busulfan, cyclophosphamide and melphalan, conditioning regimen

Group Type ACTIVE_COMPARATOR

busulfan, cyclophosphamide and melphalan, BuCyMel

Intervention Type DRUG

a three alkylator combination of busulfan, cyclophosphamide and melphalan (BuCyMel, standard arm)

CloFluBu

a combination of clofarabine, fludarabine and busulfan conditioning regimen

Group Type EXPERIMENTAL

clofarabine, fludarabine and busulfan, CloFluBu

Intervention Type DRUG

combination of clofarabine, fludarabine and busulfan in which two alkylators are replaced by antimetabolites (CloFluBu, experimental arm)

Interventions

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busulfan, cyclophosphamide and melphalan, BuCyMel

a three alkylator combination of busulfan, cyclophosphamide and melphalan (BuCyMel, standard arm)

Intervention Type DRUG

clofarabine, fludarabine and busulfan, CloFluBu

combination of clofarabine, fludarabine and busulfan in which two alkylators are replaced by antimetabolites (CloFluBu, experimental arm)

Intervention Type DRUG

Other Intervention Names

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BuCyMel CloFluBu

Eligibility Criteria

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Inclusion Criteria

* Age ≤18 years at time of initial AML, age ≤ 21 years at transplantation.
* HCT is performed in a study participating center
* All women of childbearing potential who have to have a negative pregnancy test within 2 weeks prior to the start of treatment.
* Signed informed consent.
* 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).
* In hematological remission, defined as:

\< 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 and no evidence of extramedullary disease, including in CNS and no leukemic blasts in the peripheral blood (verified by flow cytometry in case immature cells are detected in the peripheral blood differential).

-Patients must have a related or unrelated donor fulfilling any of the following criteria: HLA 10/10 allelic matched, identical, sibling BM donor or HLA 10/10 or 9/10 allelic matched related/unrelated BM or PBSC donor orHLA 5-6/6 unrelated or 6-7-8/8 unrelated Cord Blood (UCB)


* Diagnosis of acute myeloid leukemia
* Indication for allogeneic stem cell transplantation, as defined by primary treatment protocol or treating physician.
* Age ≤18 years at time of initial AML, age ≤ 21 years at transplantation.
* Signed informed consent to prospectively register follow-up data.

Exclusion Criteria

* Diagnosis of myelodysplastic syndrome (MDS).
* Diagnosis of juvenile myelomonocytic leukemia (JMML).
* History of previous malignancy (AML diagnosed as secondary cancer).
* Known diagnosis of Fanconi anemia.
* Prior autologous or allogeneic hematopoietic stem cell transplant.
* Planned prophylactic DLI or other immunotherapeutic interventions after HCT that are not included in the upfront protocol, Planned anti-leukemic medication after HCT that are not included in the upfront protocol
* Known intolerance to any of the chemotherapeutic drugs in the protocol.
* Major organ failure precluding administration of planned chemotherapy.
* Patients with uncontrolled bacterial, viral, or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
* 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.
* Karnofsky / Lansky score \< 50%
* Females who are pregnant (positive serum or urine βHCG) or breastfeeding.
* Females of childbearing potential or men who have sexual contact with females of childbearing potential unwilling to use effective forms of birth control or abstinence for one year after transplantation.
* Subjects unwilling or unable to comply with the study procedures.


* Diagnosis of Myelodysplastic syndrome (MDS).
* Diagnosis of Juvenile myelomonocytic leukemia (JMML).
* Age above 21 years at time of transplantation
* No consent is given to prospectively register outcome data
* Prior autologous or allogeneic hematopoietic stem cell transplant.
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vastra Gotaland Region

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Karin Mellgren, Prof. MD

Role: STUDY_CHAIR

Sahlgrenska University Hospital

Birgitta Versluys, MD, Phd

Role: PRINCIPAL_INVESTIGATOR

Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

Locations

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L'Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)

Brussels, , Belgium

Site Status NOT_YET_RECRUITING

Cliniques Universitaires Saint-Luc (CUSL)

Brussels, , Belgium

Site Status NOT_YET_RECRUITING

Department of Pediatric Hematology, Oncology and SCT, Ghent University Hospital

Ghent, , Belgium

Site Status NOT_YET_RECRUITING

University Hospital Leuven

Leuven, , Belgium

Site Status NOT_YET_RECRUITING

Centre Hospitalier Régional de la Citadelle (CHR)/CHU Liège

Liège, , Belgium

Site Status NOT_YET_RECRUITING

Paediatric Stem Cell Transplant and Immune Deficiency, Department of Pediatric and Adolescent Medicine, Section 4072, Rigshospitalet University Hospital of Copenhagen

Copenhagen, , Denmark

Site Status RECRUITING

Division of Hematology, Oncology, and Stem Cell Transplantation, The New Children's Hospital, Helsinki University Hospital

Helsinki, , Finland

Site Status RECRUITING

Department of Pediatrics and Adolescent Medicine, Hong King Children's Hospital

Hong Kong, , Hong Kong

Site Status NOT_YET_RECRUITING

Schneider Children's Medical Center of Israel

Petah Tikva, , Israel

Site Status NOT_YET_RECRUITING

Vilnius University Hospital Santaros Klinikos Center for Pediatric Oncology and Hematology

Vilnius, , Lithuania

Site Status NOT_YET_RECRUITING

Princess Máxima Center for Pediatric Oncology

Utrecht, , Netherlands

Site Status RECRUITING

Department of Pediatric Hematology and Oncology, Oslo University HospitalOslo University Hospital

Oslo, , Norway

Site Status RECRUITING

Stemcelltransplant unit Hospital Niño Jesús

Madrid, , Spain

Site Status NOT_YET_RECRUITING

Queen Silvia Children's Hospital, Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status RECRUITING

Barncancercentrum, avdelning 64, Skane University Hospital

Lund, , Sweden

Site Status RECRUITING

Pediatric Hematology immunology and stem cell transplantation Astrid Lindgren children's Hospital Huddinge K86-88

Stockholm, , Sweden

Site Status NOT_YET_RECRUITING

Childrens department for Blood and tumor diseases Uppsala University Hospital

Uppsala, , Sweden

Site Status NOT_YET_RECRUITING

Countries

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Belgium Denmark Finland Hong Kong Israel Lithuania Netherlands Norway Spain Sweden

Central Contacts

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Karin Mellgren, Prof. MD

Role: CONTACT

Phone: +46 (0)31 3421000

Email: [email protected]

Anna M Schröder Håkansson, RN

Role: CONTACT

Phone: +46 (0) 761141327

Email: [email protected]

Facility Contacts

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Pauline Mazilier, MD, PhD

Role: primary

Yousra Hadrani

Role: backup

Cécile Boulanger, MD, PhD

Role: primary

Victoria Bordon, MD, PhD

Role: primary

Marlies Bekaert

Role: backup

Anne Uyttebroeck, MD, PhD

Role: primary

An Michiels

Role: backup

Evelyne Willems, MD, PhD

Role: primary

Catherine Sondag

Role: backup

Marianne Ifversen, MD, PhD

Role: primary

Luise Thellesen

Role: backup

Samppa Ryhänen, MD, PhD

Role: primary

Anna Blubaum, RN

Role: backup

Daniel Cheuk, MD, PhD

Role: primary

Jerry Stein, MD,PhD

Role: primary

Jelena Rascon, MD, PhD

Role: primary

Renata Blackute

Role: backup

Birgitta Versluys, MD, PhD

Role: primary

Jochen Buechner, MD, PhD

Role: primary

Marta Gonzales Vicent Gonzales Vicent, MD, PhD

Role: primary

José M Fernandez

Role: backup

Karin Mellgren, Prof.MD

Role: primary

MD, PhD

Role: backup

Kees-Jan Pronk, MD, PhD

Role: primary

Yvonne Håkansson, RN

Role: backup

Mikael Sundin, MD, PhD

Role: primary

Gunilla Olofsson, RN

Role: backup

Natalja Jackmann, MD, PhD

Role: primary

Other Identifiers

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2021-003282-36

Identifier Type: -

Identifier Source: org_study_id