AzTrials
AzTrials

Acute Myeloid Leukemia (AML) in RemissionPhase 3SCRIPT-AMLNCT05477589

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

A Phase 3 study testing busulfan, cyclophosphamide and melphalan, BuCyMel and clofarabine, fludarabine and busulfan, CloFluBu in people with Acute Myeloid Leukemia (AML) in Remission and Stem Cell Transplantation, run by Vastra Gotaland Region at 17 sites in 10 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages Up to 18 years
What is being tested?
busulfan, cyclophosphamide and melphalan, BuCyMel and clofarabine, fludarabine and busulfan, CloFluBu
Could I receive a placebo?
No, everyone receives an active treatment
How many people
170 participants
Where
17 sitesin 10 countries
Study dates
7 Jun 2022to 31 Dec 2031
Phase
Phase 3
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 Up to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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:
Show all 28Show fewer
  • < 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.
  • Not eligible for randomization, either due to lack of consent or not fulfilling inclusion criteria for interventional part of the study.
  • Signed informed consent to prospectively register follow-up data.
  • Exclusion criteria for the randomization part of the study :
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

17 sites in 10 countries. Contact the study team or a site near you to ask about taking part.

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

17 sites in 10 countries

Belgium5 sites, 5 recruiting

  • L'Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)

    Brussels, 1020

    Pauline Mazilier, MD, PhD, 0032 2 477 26 78, Pauline.mazilier@huderf.bf

    Yousra Hadrani, 0032 2 477 35 21, Yousra.Hadrani@huderf.be

    Not yet recruiting

  • Cliniques Universitaires Saint-Luc (CUSL)

    Brussels, 1200

    Cécile Boulanger, MD, PhD

    Cécile Boulanger, MD, PhD

    Not yet recruiting

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

    Ghent, 9000

    Victoria Bordon, MD, PhD, 0032 9 332 58 60, Victoria.Bordon@uzgent.be

    Marlies Bekaert, 0032 9 332 05 15, Marlies.bekaert@uzgent.be

    Not yet recruiting

  • University Hospital Leuven

    Leuven, 3000

    Anne Uyttebroeck, MD, PhD, 0032 16 34 39 72, Anne.uyttebroeck@uzleuven.be

    An Michiels, 0032 16 34 98 66, An.michiels@uzleuven.be

    Not yet recruiting

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

    Liège, 4000

    Evelyne Willems, MD, PhD, e.willems@chuliege.be

    Catherine Sondag, 0032 4 321 89 77, c.sondag@chuliege.be

    Not yet recruiting

Other trials in Belgium

Sweden4 sites, 4 recruiting

  • Queen Silvia Children's Hospital, Sahlgrenska University Hospital

    Gothenburg, 41685

    Karin Mellgren, Prof.MD, +46 (0)31 3421000, karin.mellgren@vgregion.se

    MD, PhD, +46 (0)31 3421000, cecilia.langenskiold@vgregion.se

    Recruiting

  • Barncancercentrum, avdelning 64, Skane University Hospital

    Lund, SE- 221 85

    Kees-Jan Pronk, MD, PhD, ornelis.pronk@skane.se

    Yvonne Håkansson, RN, yvonne.hakansson@skane.se

    Recruiting

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

    Stockholm, 141 86

    Mikael Sundin, MD, PhD, +46 8 585 848 43, mikael.sundin@ki.se

    Gunilla Olofsson, RN, gunilla.h.olofsson@regionstockholm.se

    Not yet recruiting

  • Childrens department for Blood and tumor diseases Uppsala University Hospital

    Uppsala, SE-751 85

    Natalja Jackmann, MD, PhD, +46 186119639, natalja.jackmann@kbh.uu.se

    Natalja Jackmann, MD, PhD

    Not yet recruiting

Other trials in Sweden

Denmark1 site, 1 recruiting

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

    Copenhagen, DK-2100

    Marianne Ifversen, MD, PhD, +45 3545 0979, Marianne.Ifversen@regionh.dk

    Luise Thellesen, +45 3545 3563, Luise.Thellesen@regionh.dk

    Recruiting

Other trials in Denmark

Finland1 site, 1 recruiting

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

    Helsinki, FIN-00290

    Samppa Ryhänen, MD, PhD, samppa.ryhanen@hus.fi

    Anna Blubaum, RN, +358 40 483 8664, anna.blubaum@hus.fi

    Recruiting

Other trials in Finland

Hong Kong1 site, 1 recruiting

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

    Hong Kong

    Daniel Cheuk, MD, PhD, cheukkld@hku.hk

    Daniel Cheuk, MD, PhD

    Not yet recruiting

Other trials in Hong Kong

Israel1 site, 1 recruiting

  • Schneider Children's Medical Center of Israel

    Petah Tikva, 4920235

    Jerry Stein, MD,PhD, 972-3-9253742, jstein@clalit.org.il

    Jerry Stein, MD, PhD

    Not yet recruiting

Other trials in Israel

Lithuania1 site, 1 recruiting

  • Vilnius University Hospital Santaros Klinikos Center for Pediatric Oncology and Hematology

    Vilnius, 08661

    Jelena Rascon, MD, PhD, +37069778361, jelena.rascon@gmail.com

    Renata Blackute, +370 698 86225, renata.blackute@gmail.com

    Not yet recruiting

Other trials in Lithuania

Netherlands1 site, 1 recruiting

  • Princess Máxima Center for Pediatric Oncology

    Utrecht, 3584CS

    Birgitta Versluys, MD, PhD, +31650006514, A.B.Versluijs@prinsesmaximacentrum.nl

    Birgitta Versluys, MD, PhD

    Recruiting

Other trials in Netherlands

Norway1 site, 1 recruiting

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

    Oslo, 0424

    Jochen Buechner, MD, PhD, +4747416023, jocbuc@ous-hf.no

    Jochen Buechner, MD, PhD

    Recruiting

Other trials in Norway

Spain1 site, 1 recruiting

  • Stemcelltransplant unit Hospital Niño Jesús

    Madrid, 28009

    Marta Gonzales Vicent Gonzales Vicent, MD, PhD, +34-915035938, martagonzalesvicent@gmail.com

    José M Fernandez, chemafer@mac.com

    Not yet recruiting

Other trials in Spain

About this study

Official title: A Randomized, Multi-Center Phase III Trial Comparing Two Conditioning Regimens (CloFluBu and BuCyMel) in Children With Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplantation.

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)

Read the detailed description

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.

Being tested
busulfan, cyclophosphamide and melphalan, BuCyMel, clofarabine, fludarabine and busulfan, CloFluBu
Keywords
Leukemia, Leukemia, Myeloid, Acute, Neoplasms, Haematopoietic cell transplantation, Paediatric
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • busulfan, cyclophosphamide and melphalan, BuCyMelDrug

    Also called BuCyMel

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

  • clofarabine, fludarabine and busulfan, CloFluBuDrug

    Also called CloFluBu

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

Study groups in NCT05477589
Study groupRoleWhat they receive
BuCyMelActive comparatora combination of busulfan, cyclophosphamide and melphalan, conditioning regimen
Receives: Drug: busulfan, cyclophosphamide and melphalan, BuCyMel
CloFluBuExperimentala combination of clofarabine, fludarabine and busulfan conditioning regimen
Receives: Drug: clofarabine, fludarabine and busulfan, CloFluBu

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: 2 years

Secondary outcomes (19)

  1. Neutrophil and platelet engraftment

    time to engraftment after stem cells transplantation, in all patients

    Measured: 28 days post transplantation

  2. Primary graft failure

    The incidence of graft failure defined as neutrophil recovery by day +28 post transplantation

    Measured: +28 days post transplantation

  3. Secondary graft failure

    The incidence of secondary graft failure

    Measured: 2 years

  4. Cumulative incidence of relapse

    The incidence of cumulative incidence of relapse during the first two years after transplantation

    Measured: 2 years

  5. The association between pre-HCT MRD and relapse

    % of remaining leukemic cells in the last bone marrow sample taken before start of conditioning

    Measured: 2 years

  6. Cumulative incidence of transplant-related mortality

    The incidence of transplant-related mortality at 2 years

    Measured: 2 years

  7. Disease-free survival

    Disease-free survival at 2 years

    Measured: 2 years

  8. Overall survival

    Overall survival at 2 years

    Measured: 2 years

  9. Immunological recovery

    Immunological recovery of CD3+ and CD4+ cells in peripheral blood

    Measured: 2 years

  10. Incidence of grade II-IV and III-IV acute GVHD

    The incidence of acute GvHD

    Measured: +180 days post transplantation

  11. Incidence of chronic GVHD

    The incidence of cGVHD

    Measured: 2 years

  12. Incidence of grade ≥ 3 toxicity Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease

    The rates of grade ≥ 3 Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease

    Measured: + 100 days post transplantation

  13. Incidence of grade ≥ 3 toxicity Engraftment Syndrome (ES)

    The incidence of engraftment syndome

    Measured: 2 years

  14. Incidence of grade ≥ 3 toxicity Transplant-associated thrombotic microangiopathy (TA-TMA)

    The incidence of TA-TMA

    Measured: 2 years

  15. Incidence of grade ≥ 3 toxicity Hemorrhagic Cystitis (HC)

    The incidence of HC

    Measured: 2 years

  16. Incidence of grade ≥ 3 infections

    The incidence of grade ≥ 3 infections of bacterial, viral and fungal origin

    Measured: 2 years

  17. Health-Related Quality of Life, HRQoL.

    HRQoL will be measured at baseline and at certain intervals using the quality of life instrument EQ-5D-Y, (Youth)™which include 2 measurements, the descriptive scale ( i.g. the score 1 is no problems and 3 is a lot of problems) and the VAS scale( 1 is the worst health and 100 is the best health that day).

    Measured: 2 years

  18. Transplant-associated hormonal and gonadal late effects

    the date of spontaneous puberty, date of spontaneous menarche for female patients and mean testicular volume for male patients, use of hormonal replacement therapy and use of fertility preservation

    Measured: 2 years

  19. Nutritional status

    BMI in kg/m^2 at baseline and post transplantation

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2022
  2. Study start7 Jun 2022
  3. Primary completion31 Dec 2029 (estimated)
  4. Study completion31 Dec 2031 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Model description
AML patient eligible for stem cells transplantation will be randomized either get conditioning regimens CloFluBu or BuCyMel.
Masking
None (open label)
Enrolment
170 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05477589
Sponsor's protocol ID
2021-003282-36
Acronym
SCRIPT-AML
Status last verified
Nov 2024
First submitted
13 Jul 2022
Last updated
19 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing busulfan, cyclophosphamide and melphalan, BuCyMel and clofarabine, fludarabine and busulfan, CloFluBu in people with Acute Myeloid Leukemia (AML) in Remission and Stem Cell Transplantation, run by Vastra Gotaland Region at 17 sites in 10 countries.

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 28 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 19 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Belgium, Sweden, Denmark, Finland, Hong Kong and 5 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 Karin Mellgren, Prof. MD (+46 (0)31 3421000, karin.mellgren@vgregion.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

2-year, acute grade III to IV-free, chronic non-limited GvH-free, relapse-free survival (GREF) (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05477589.

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 Dec 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in