International study for the treatment of children and adolescents with relapse of acute lymphoblastic leukemia (ALL) at high risk
Summary description of the study
Acute lymphoblastic leukemia (ALL) is the most common type of blood cancer in childhood and adolescence. By conducting international studies, the prognosis of ALL has been significantly improved. However, the prognosis is lower when a relapse of ALL occurs, meaning when a patient becomes ill with ALL again. Therefore, the main goal of this study is to further improve the survival and cure rate of children and adolescents with relapse of ALL. The study investigates the efficacy of the new drug Bortezomib. Bortezomib can, together with other medications, prevent cancer cells from multiplying and kill them. It is now to be tested in a large study whether Bortezomib, together with standard therapy, works better than standard therapy alone, thus improving treatment outcomes in children and adolescents.
(BASEC)
Intervention under investigation
The treatment concept of this study is intended for children and adolescents at high risk for recurrence of ALL. Participating patients will be randomly assigned to two groups. Both receive the same standard chemotherapy over a period of about four months. One patient group additionally receives the new drug Bortezomib. At the beginning of the study period, patients are allocated in a 2:1 ratio to the two arms, with twice as many patients in the Bortezomib arm. Since many patients have already been treated in the standard induction arm without Bortezomib in the past, this study can place more weight on the experimental arm. If, during the course of the study, planned interim evaluations reveal a potential advantage of one of the two arms (standard therapy with or without Bortezomib), more patients will be assigned in the randomization to the potentially advantageous study arm. If one arm proves to be clearly superior or inferior, the randomization will be stopped, and all patients will receive the proven superior therapy. This process is monitored by an independent expert group. With this approach, it is possible to reliably determine whether adding Bortezomib to the induction therapy improves cure rates or merely adds side effects without providing a benefit to the patients.
In the event of a relapse, the extent of the disease must be determined. Therefore, a bone marrow puncture (up to 5 ml of bone marrow blood from the right and left side - a total of up to 10 ml) and a lumbar puncture are necessary. If there is suspicion of involvement of other organs, additional diagnostic measures may be required. The material obtained during diagnostics is examined in specialized laboratories (reference laboratories) to ensure that internationally accepted standards and quality assurance are adhered to. All bone marrow and cerebrospinal fluid collections comply in nature and extent with the routine measures that would also be performed outside the study in identical form. As part of this study, to determine the blood levels of Asparaginase, an additional approximately 4 ml of blood is taken before each administration of PEG-Asparaginase and 7 and 14 days after administration. For patients receiving Bortezomib, after consultation and consent, 5 ml of blood will be taken after 12 and 48 hours to measure the drug level. They are to confirm the well-studied degradation of the drug in adults in children in the combination intended for this therapy.
The performance of a pregnancy test (additional measurement as part of routine blood collection) in adolescent women of childbearing age and the initially weekly neurological status (as part of the routine physical examination) are study-specific measures. All other measures will be performed as part of clinical routine independently of the study.
(BASEC)
Disease under investigation
Relapse of acute lymphoblastic leukemia (ALL)
(BASEC)
Confirmed diagnosis of relapse of acute lymphoblastic leukemia Patient under 18 years of age Classification into high-risk group (BASEC)
Exclusion criteria
BCR-ABL/ t(9;22) positive ALL Pregnancy or positive pregnancy test Severe comorbidities that, in the opinion of the investigator, do not allow treatment according to the protocol (BASEC)
Trial sites
Aarau, Basel, Bellinzona, Bern, Geneva, Lausanne, Luzern, St. Gallen, Zurich
(BASEC)
Sponsor
Charité - Universitätsmedizin Berlin Swiss Paediatric Oncology Group SPOG
(BASEC)
Contact
Contact Person Switzerland
Prof. Dr. med. Jean-Pierre Bourquin
+41 44 249 57 16
jean-pierre.bourquin@clutterkispi.uzh.chUniversitäts-Kinderspital Zürich
(BASEC)
General Information
Charit? - Universit?tsmedizin Berlin
+4930450 666 833
jean-pierre.bourquin@clutterkispi.uzh.ch(ICTRP)
Scientific Information
Charit? - Universit?tsmedizin Berlin
+4930450 666 833
jean-pierre.bourquin@clutterkispi.uzh.ch(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
18.04.2019
(BASEC)
ICTRP Trial ID
EUCTR2012-000810-12 (ICTRP)
Official title (approved by ethics committee)
International Study for Treatment of High Risk Childhood Relapsed ALL 2010 A randomized Phase II Study Conducted by the Resistant Disease Committee of the International BFM Study Group (BASEC)
Academic title
IntReALL HR 2010International Study for Treatment of High Risk Childhood Relapsed ALL 2010 - IntReALL-HR-2010 (ICTRP)
Public title
IntReALL HR 2010International Study for Treatment of Standard Risk Childhood Relapsed Acute Lymphoblastic Leukemia 2010 (ICTRP)
Disease under investigation
Acute lymphoblastic leukemia (ALL);Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)
Intervention under investigation
Trade Name: Velcade
Product Name: Velcade
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: BORTEZOMIB
CAS Number: 179324-69-7
Other descriptive name: VELCADE
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 3,5-
Product Name: Asparaginase
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Asparaginase
CAS Number: 9015-68-3
Other descriptive name: ASPARAGINASE
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 5000-
Product Name: Dexamethasone
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Dexamethasone
Other descriptive name: DEXAMETHASONE BASE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 3.3-
Product Name: Vincristine
Pharmaceutical Form: Solution for injection
INN or Proposed INN: VINCRISTINE SULFATE
Other descriptive name: VINCRISTINE SULFATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-
Product Name: Methotrexate
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: METHOTREXATE
CAS Number: 59-05-2
Other descriptive name: METHOTREXATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-
Product Name: Mitoxantrone
Pharmaceutical Form: Concentrate and solvent for solution for injection/infusion
INN or Proposed INN: MITOXANTRONE HYDROCHLORIDE
CAS Number: 70476-82-3
Other descriptive name: MITOXANTRONE HYDROCHLORIDE PH. EUR.
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
(ICTRP)
Type of trial
Interventional clinical trial of medicinal product (ICTRP)
Trial design
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2 (ICTRP)
Inclusion/Exclusion criteria
Gender:
Female: yes
Male: yes
Inclusion criteria:
- Morphologically confirmed diagnosis of 1st relapsed precursor B-cell or T-cell ALL
- Children less than 18 years of age at date of inclusion into the study
- Meeting HR criteria
- Patient enrolled in a participating centre
- Written informed consent
- Start of treatment falling into the study period
- No participation in other clinical trials 30 day prior to study enrolment that interfere with this protocol, except trials for primary ALL
Are the trial subjects under 18? yes
Number of subjects for this age range: 250
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
(ICTRP)
Exclusion criteria:
- BCR-ABL/ t(9;22) positive ALL
- Pregnancy or positive pregnancy test (urine sample positive for ?-HCG > 10 U/l)
- Sexually active adolescents not willing to use highly effective contraceptive method (pearl
index <1) until 2 years after end of anti-leukemic therapy
- Breast feeding
- Relapse post allogeneic stem-cell transplantation
- Neuropathy > II
- The whole protocol or essential parts are declined either by patient himself/herself or the
respective legal guardian
- No consent is given for saving and propagation of pseudonymized medical data for study
reasons
- 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)
- Subjects unwilling or unable to comply with the study procedures
- Subjects who are legally detained in an official institute
Primary and secondary end points
Main Objective: Improvement of CR rates after induction with ALL R3 with bortezomib versus without bortezomib.;Secondary Objective: Improvement of EFS and OS rates
Improvement of MRD reduction after induction with versus without bortezomib
Toxicity of induction with versus without bortezomib
Efficacy of consolidation elements to reduce MRD load until allo-HSCT;Primary end point(s): Randomized induction trial: Improvement of CR2 rates with standard chemotherapy + Bortezomib (Arm B) quantified by cytology compared with standard chemotherapy (Arm A);Timepoint(s) of evaluation of this end point: Primary endpoint will be evaluated at week 5 after induction. (ICTRP)
Secondary end point(s): Two years EFS and OS, rate of patients reaching HSCT, MRD rates post induction and pre-HSCT, toxicity of randomized arms, toxicity of consolidation until HSCT;Timepoint(s) of evaluation of this end point: - EFS, OS: two years after recruitment is completed
- toxicity: together with the primary endpoint
- MRD rates: 9 weeks after primary endpoint (ICTRP)
Registration date
06.04.2018 (ICTRP)
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Dept of Pediatric Oncology/Hematolo, arend.stackelberg@charite.de, +4930450 666 833, Charit? - Universit?tsmedizin Berlin (ICTRP)
Secondary trial IDs
IntReALL-HR-2010, 2012-000810-12-SE (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000810-12 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available