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Treosulfan-based Conditioning in Paediatric Patients With Haematological Malignancies | Clinical Trials | Clareo Health

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Treosulfan-based Conditioning in Paediatric Patients With Haematological Malignancies

Clinical Phase II Trial to Describe the Safety and Efficacy of Treosulfan-based Conditioning Therapy Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Paediatric Patients With Haematological Malignancies

NCT02333058•medac GmbH

View on ClinicalTrials.gov

Summary

The primary goal of this study is to evaluate an alternative myeloablative, but reduced toxicity conditioning regimen in children, to describe the safety and efficacy of intravenous (i.v.) Treosulfan administered as part of a standardised Fludarabine-containing conditioning and to contribute to the current pharmacokinetic model to be able to finally give age (or body surface area) dependent dose recommendations. The treatment regimens given in the protocol MC-FludT.17/M are based on sufficient clinical safety and efficacy data. Considering the vital indication for allogeneic haematopoietic stem cell transplantation of the selected patient population, the risk-benefit assessment is therefore reasonably in favour of the study conduct.

Detailed Description

The protocol MC-FludT.17/M is a clinical phase II trial to describe the safety and efficacy of Treosulfan-based conditioning therapy prior to allogeneic haematopoietic stem cell transplantation (allo-HSCT) in at least 70 paediatric patients with haematological malignancies (male and female children with haematological malignant diseases as acute lymphoblastic leukaemias (ALL), acute myeloid leukaemias (AML), myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukaemias (JMML), requiring myeloablative conditioning treatment with following allo-HSCT). Treosulfan dose per day is to be calculated by using body surface area (BSA). Two background conditioning regimens with Treosulfan are allowed: One regimen consists of a standardised Fludarabine-containing regimen and the other consists of an intensified regimen with Fludarabine and ThioTEPA. Freedom from transplant (treatment)-related mortality (TRM), defined as death from any transplant-related cause from the day of first administration of study medication until day +100 after HSCT is the primary objective of the trial. Moreover, the current pharmacokinetic (PK) model should be contributed to be able to finally give age (or BSA) dependent dose recommendations.

Eligibility

Age

0 - 17 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Haematological malignant disease i.e. ALL, AML, MDS or JMML, indicated for allo-HSCT.
•2. Indication for first allo-HSCT or second allo-HSCT due to disease relapse, graft failure, or secondary malignancy after previous HSCT.
•3. Available matched sibling donor (MSD), matched family donor (MFD) or matched unrelated donor (MUD). For bone marrow (BM) and peripheral blood (PB) match is defined as 9/10 or 10/10 allele match after four digit typing in human leucocyte antigens (HLA)-A, B, C, DRB1 and DQB1.
•4. Patients with ALL or AML in complete morphologic remission (blast counts \<5 % in BM) and patients with MDS or JMML with blast counts \< 20 % in BM at study entry.
•5. Age at time of registration from 28 days to less than 18 years of age.
•6. Lansky (patients aged \<16 years) or Karnofsky (patients aged ≥ 16 years) performance score of at least 70 %.
•7. Written informed consent of the parents/ legal guardians and patient's assent/consent according to national regulations.
•8. Females of child-bearing potential or male patients' partners with child-bearing potential must use a highly effective method of contraception (pearl index \< 1 %) such as complete sexual abstinence, combined oral contraceptive, hormone intrauterine contraceptive device (IUCD), vaginal hormone ring, transdermal contraceptive patch, contraceptive implant or depot contraceptive injection in combination with a second method of contraception like a condom or a cervical cap / diaphragm with spermicide or surgical sterilisation (vasectomy) in male patients or male partners during the study and at least 6 months thereafter.
•9. Negative pregnancy test for females of child-bearing potential.

Exclusion Criteria

•1. Third or later allo-HSCT.
•2. HSCT from haploidentical or umbilical cord blood donor.
•3. Symptomatic involvement of central nervous system (CNS) at study entry.
•4. Treatment with cytotoxic drugs within 10 days prior to day 7.
•5. Obese paediatric patients with body mass index: weight (kg)/\[height (m)\]² \> 30 kg/m².
•6. Solid tumours (e.g. neuroblastoma, peripheral neuroectodermal tumour \[PNET\], Ewing sarcoma).
•7. Fanconi anaemia and other deoxyribonucleic acid (DNA) breakage repair disorders.
•8. Impaired liver function indicated by Bilirubin \> three times the upper limit of normal (ULN) or aspartate aminotransferase/alanine aminotransferase (AST/ALT) \> five times ULN, or active infectious hepatitis.
•9. Impaired renal function indicated by estimated glomerular filtration rate (\[GFR\], according to the Schwartz formula) \< 60 mL/min/1,73m2.
•10. Impaired cardiac function: severe cardiac insufficiency indicated by left ventricle ejection fraction (LVEF) \< 35 %.
+5 more criteria

Locations (24)

St. Anna Children Hospital

Vienna, Austria

University Hospital Motol, Charles University, Prague

Prague, Czechia

University Clinic Düsseldorf

Düsseldorf, Germany

University Clinic Erlangen-Nürnberg

Erlangen, Germany

Universitätsklinikum Essen

Essen, Germany

University Hospital Johann Wolfgang Goethe

Frankfurt, Germany

University Clinic Hamburg-Eppendorf

Hamburg, Germany

Medical University Hannover

Hanover, Germany

University Clinic Heidelberg

Heidelberg, Germany

University Clinic Jena

Jena, Germany

Key Dates

Start Date

November 21, 2014

Primary Completion Date

December 24, 2016

Completion Date

September 30, 2019

Last Updated

May 4, 2020

Enrollment

ACTUAL participants

Conditions

Acute Lymphoblastic Leukaemias (ALL)Acute Myeloid Leukaemias (AML)Myelodysplastic Syndromes (MDS)Juvenile Myelomonocytic Leukaemias (JMML)

Interventions

Treosulfan

DRUG

Darzalex Faspro (Daratumumab and Hyaluronidase-fihj) Before Standard Desensitization and Allogeneic Peripheral Blood Stem Cell Transplantation in Adult Patients at High-risk for Primary Graft Failure Secondary to Donor Specific Antibodies

NCT06398457

Hematologic MalignancyBone Marrow Transplant Rejection+10 more

View study

RECRUITINGNA

Involvement of CDA and/or dCK Metabolizing Enzymes in the Response to Azacytidine Treatment of Patients With Hematologic Malignancies

NCT06886425

Myelodysplastic Syndromes (MDS)Leukemia Acute Myeloid - AML

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 4, 2020Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Treosulfan-based Conditioning in Paediatric Patients With Haematological Malignancies

Inclusion Criteria

Exclusion Criteria

Darzalex Faspro (Daratumumab and Hyaluronidase-fihj) Before Standard Desensitization and Allogeneic Peripheral Blood Stem Cell Transplantation in Adult Patients at High-risk for Primary Graft Failure Secondary to Donor Specific Antibodies

Involvement of CDA and/or dCK Metabolizing Enzymes in the Response to Azacytidine Treatment of Patients With Hematologic Malignancies

A Multi-center Retrospective Study of INO Treating B-ALL

Phase 1-2 MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell

Panobinostat Maintenance After HSCT fo High-risk AML and MDS

Safety, Pharmacokinetics, and Pharmacodynamics of Oral Azacitidine in Subjects With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myelogenous Leukemia