This study has been transitioned to CTIS with ID 2024-513070-21-00 check the CTIS register for the current data. Primary objectives: Improvement of CR2 rates after induction with ALL R3 with bortezomib versus withoutbortezomib in HR relapsed ALL…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Randomized induction trial:
*Rates of CR2 with standard chemotherapy + Bortezomib (Arm B) compared with
standard chemotherapy (Arm A), quantified by cytology
Secondary outcome
*Three years EFS and OS
*Rate of patients reaching HSCT
*MRD rates post-induction and pre-HSCT
*Prognostic relevance of MRD pre HSCT, CR2 and MRD rates during consolidation
*Toxicity of randomized arms
Background summary
Although survival of children with acute lymphoblastic leukemia (ALL) has
considerably improved over the past few decades, relapsed ALL remains a leading
cause of mortality in children with cancer. Risk has been defined by the
International BFM Study Group (I-BFM-SG) based on duration of first remission,
immunophenotype of malignant clone, and site of relapse. Patients classified as
high risk (HR) by these criteria have poor response rates to standard induction
therapy, high rates of subsequent relapse and require an allogeneic
hematopoetic stem cell transplantation (allo-HSCT) for consolidation of 2nd
remission. Over the last decade members of the I-BFM-SG have investigated the
use of different combinations of conventional cytotoxic agents. Even with
allo-HSCT, none of these approaches have improved outcome above 40%. Therefore,
for HR patients there is a need to investigate the curative potential of new
agents combined with systemic therapy. The proteasome inhibitor bortezomib has
shown synergistic activity with acceptable toxicity when combined with
corticosteroids, anthracyclines and alkylating agents in adult patients with
cancer as well as with dexamethasone, doxorubicin, vincristine and
PEG-asparaginase in children with refractory or relapsed ALL. In the I-BFM-SG
IntReALL HR 2010 study, the potential of Bortezomib combined with a modified
ALL R3 backbone as induction regimen for HR patients to improve CR2 rates will
be investigated in a randomized phase II design. Induction is followed by
conventional intensive consolidation.
Study objective
This study has been transitioned to CTIS with ID 2024-513070-21-00 check the CTIS register for the current data.
Primary objectives:
Improvement of CR2 rates after induction with ALL R3 with bortezomib versus
without
bortezomib in HR relapsed ALL patients
Secondary objectives:
Improvement of Event Free Survival (EFS) and overall survival (OS) rates
Improvement of minimal residual disease (MRD) reduction after induction with
versus without bortezomib
Improvement of MRD load prior to SCT
Increasing the proportion of HR patients reaching SCT
Prognostic relevance of MRD pre SCT
Improvement of CR2 and/or MRD rates during consolidation
Toxicity of induction with versus without bortezomib
Study design
The IntReALL HR 2010 trial is an inter-group, international multi-centre,
treatment optimization trial. It contains the following treatment arms:
- induction: prospective, randomized, adaptive, open label phase II trial
comparing arm A (modified ALL R3) versus arm B (modified ALL R3 + Bortezomib)
- post-induction single arm observational trial with intensive multidrug
chemotherapy courses HC1 (modified AIEOP-BFM ALL 2009 HR1), HC2 (modified HR3).
This is the current treatment in The Netherlands
- a third post-induction chemotherapy block HC3 (modified AIEOP-BFM ALL HR2)
may optionally be given within the IntReALL HR 2010 trial or used as standard
comparator for an investigational window trial.
- all patients in morphological CR2 will be subjected to allogeneic HSCT
- termination of the trial after completion of the 2nd or 3rd consolidation
block before investigational window trial and/or allogeneic HSCT. Follow-up
will be done until reaching secondary EFS / OS endpoints.
- patients with insufficient treatment response (MRD >= 10-3 after induction)
may be allocated to individualized consolidation therapy based on individual
biologic features of the leukemia, if such approaches are available
Intervention
Randomization during remission induction treatment between standard remission
induction treatment (ALL-R3) with or without Bortezomib
Study burden and risks
Participation in the trial does not result in additional investigations as
compared to the standard treatment of children with relapsed ALL.
The risk of increased toxicity by adding Bortezomib to the standard ALL-R3
remission induction is considered to be low and will be closesly monitored by
the pharmacovigilance system established within the IntReALL group. Strict
stopping rules apply. The induction randomization implies realistic potential
to improve remission, EFS and at the end cure rates in this unfavourable
patient group with an acceptable and closely monitored risk for increased
toxicity.
Augustenburger Platz 1
Berlijn 13353
DE
Augustenburger Platz 1
Berlijn 13353
DE
Listed location countries
Age
Inclusion criteria
Relapsed precursor B-cell or T-cell ALL
Children less than 18 years
High-risk relapse (in study-protocol defined criteria)
Written informed consent
Exclusion criteria
BCR/ABL positive ALL
Pregnancy/breast feeding
Relapse post stemcell transplant
No consent
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-513070-21-00 |
| EudraCT | EUCTR2012-000810-12-NL |
| ClinicalTrials.gov | NCT03590171 |
| CCMO | NL67089.041.19 |