Treosulfan-based Conditioning in Paediatric Patients With Haematological Malignancies

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02333058
• Date of registration: 22/12/2014
• Prospective Registration: No
• Primary sponsor: medac GmbH
• Public title: Treosulfan-based Conditioning in Paediatric Patients With Haematological Malignancies
• Scientific title: 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
• Date of first enrolment: November 21, 2014
• Target sample size: 70
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02333058
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Austria, Czech Republic, Czechia, Germany, Italy, Netherlands, Poland, United Kingdom

Contacts

• Name: Ajay Vora, MD, Prof.
• Affiliation: Great Ormond Street Hospital NHS Trust

Key inclusion & exclusion criteria

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 %.

11. Requirement for supplementary continuous oxygen.

12. Severe active infection requiring deferral of conditioning.

13. Human immunodeficiency virus (HIV) positivity.

14. Known pregnancy, breast feeding.

15. Known hypersensitivity to Treosulfan and/or Fludarabine.



Age minimum: N/A
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Juvenile Myelomonocytic Leukaemias (JMML)

Myelodysplastic Syndromes (MDS)

Acute Lymphoblastic Leukaemias (ALL)

Acute Myeloid Leukaemias (AML)

Intervention(s)

Drug: Treosulfan

Primary Outcome(s)

Freedom from transplant (treatment)-related mortality (TRM) [Time Frame: from the day of first administration of study medication until day +100 after HSCT]

Secondary Outcome(s)

Non relapse mortality (NRM), transplant related mortality (TRM), graft failure rate, incidence of relapse/progression, relapse-free/progression-free survival (RFS/PFS) and overall survival (OS) [Time Frame: after 12 months after HSCT and until the end of the longer-term follow-up phase]

Safety including early toxicity until day +100 after HSCT, serious adverse reactions (SARs) until the end of the longer-term follow-up phase [Time Frame: until 12 months after HSCT]

Hepatic sinusoidal obstruction syndrome (HSOS), lung toxicity (CTCAE term pulmonary fibrosis), hepatic toxicity and infections of any CTCAE grade (non-serious and serious) [Time Frame: until day +100 after HSCT]

Donor-type chimerism [Time Frame: on day +28, day +100 and 12 months after HSCT]

Engraftment after HSCT [Time Frame: until engraftment]

Incidence and severity of acute (until day +100) and chronic (until 12 months after HSCT) graft versus host disease (aGvHD/cGvHD) [Time Frame: until 12 months after HSCT]

Use of rescue therapies including donor-lymphocyte infusions (DLIs) and further conditioning regimens [Time Frame: until 12 months after HSCT]

PK parameters of Treosulfan and its epoxides [Time Frame: day -6 prior to HSCT]

Secondary ID(s)

MC-FludT.17/M

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Celerion

Syneos Health