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

NCT05477589 | Recruiting Phase 3 DMC

• 1 other identifier: 2021-003282-36
• Study Type: interventional
• Target: 170
• Locations: 10 countries
• Sites: 17

Brief Summary

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)

Conditions

Acute Myeloid Leukemia (AML) in Remission; Stem Cell Transplantation

Keywords

Leukemia; Leukemia, Myeloid, Acute; Neoplasms; Haematopoietic cell transplantation; Paediatric

Outcome Measures

Primary Outcomes (1)

• 2-year, acute grade III to IV-free, chronic non-limited GvH-free, relapse-free survival (GREF)

  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)

  2 years

Secondary Outcomes (19)

• Neutrophil and platelet engraftment

  28 days post transplantation

• Primary graft failure

  +28 days post transplantation

• Secondary graft failure

  2 years

• Cumulative incidence of relapse

  2 years

• The association between pre-HCT MRD and relapse

  2 years

Study Arms (2)

BuCyMel

ACTIVE COMPARATOR

a combination of busulfan, cyclophosphamide and melphalan, conditioning regimen

Drug: busulfan, cyclophosphamide and melphalan, BuCyMel

CloFluBu

EXPERIMENTAL

a combination of clofarabine, fludarabine and busulfan conditioning regimen

Drug: clofarabine, fludarabine and busulfan, CloFluBu

Interventions

busulfan, cyclophosphamide and melphalan, BuCyMel DRUG

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

Also known as: BuCyMel

BuCyMel

clofarabine, fludarabine and busulfan, CloFluBu DRUG

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

Also known as: CloFluBu

CloFluBu

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Vastra Gotaland Region: lead

Study Sites (17)

L'Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)

Brussels, 1020, Belgium

NOT YET RECRUITING

Cliniques Universitaires Saint-Luc (CUSL)

Brussels, 1200, Belgium

NOT YET RECRUITING

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

Ghent, 9000, Belgium

NOT YET RECRUITING

University Hospital Leuven

Leuven, 3000, Belgium

NOT YET RECRUITING

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

Liège, 4000, Belgium

NOT YET RECRUITING

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

Copenhagen, DK-2100, Denmark

RECRUITING

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

Helsinki, FIN-00290, Finland

RECRUITING

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

Hong Kong, Hong Kong

NOT YET RECRUITING

Schneider Children's Medical Center of Israel

Petah Tikva, 4920235, Israel

NOT YET RECRUITING

Vilnius University Hospital Santaros Klinikos Center for Pediatric Oncology and Hematology

Vilnius, 08661, Lithuania

NOT YET RECRUITING

Princess Máxima Center for Pediatric Oncology

Utrecht, 3584CS, Netherlands

RECRUITING

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

Oslo, 0424, Norway

RECRUITING

Stemcelltransplant unit Hospital Niño Jesús

Madrid, 28009, Spain

NOT YET RECRUITING

Queen Silvia Children's Hospital, Sahlgrenska University Hospital

Gothenburg, 41685, Sweden

RECRUITING

Barncancercentrum, avdelning 64, Skane University Hospital

Lund, SE- 221 85, Sweden

RECRUITING

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

Stockholm, 141 86, Sweden

NOT YET RECRUITING

Childrens department for Blood and tumor diseases Uppsala University Hospital

Uppsala, SE-751 85, Sweden

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia; Neoplasms

Interventions

Busulfan; Cyclophosphamide; Melphalan; Clofarabine; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Study Officials

• Karin Mellgren, Prof. MD

  Sahlgrenska University Hospital

  STUDY CHAIR

• Birgitta Versluys, MD, Phd

  Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karin Mellgren, Prof. MD

CONTACT

+46 (0)31 3421000; karin.mellgren@vgregion.se

Anna M Schröder Håkansson, RN

CONTACT

+46 (0) 761141327; anna.schroder_hakansson@vgregion.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: AML patient eligible for stem cells transplantation will be randomized either get conditioning regimens CloFluBu or BuCyMel.

Study Record Dates

• First Submitted: July 13, 2022
• First Posted: July 28, 2022
• Study Start: June 7, 2022
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2031
• Last Updated: December 19, 2024

Record last verified: 2024-11

Locations

LI (1); NO (1); FI (1); SE (4); IL (1); HK (1); BE (5); NL (1); DK (1); ES (1)