International Study for Treatment of High Risk Childhood Relapsed ALL 2010

Charité University Medicine Berlin

Status and phase

Enrolling

Phase 2

Conditions

Acute Lymphoblastic Leukemia (ALL)

Treatments

Drug: Bortezomib

Study type

Interventional

Funder types

Other

NETWORK

Identifiers

NCT03590171

IntReALL HR 2010

Details and patient eligibility

About

The main goal of this study is to improve the outcome of children and adolescents with acute lymphoblastic leukemia with high risk first relapse by optimization of treatment strategies within a large international trial and the integration of new agents.

Full description

Though 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 (I) Berlin, Frankfurt, Münster (BFM) Study Group (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 polyethylene glycol (PEG) asparaginase in children with refractory or relapsed ALL. In the I-BFM-SG International Study for Treatment of High Risk Childhood Relapsed ALL (IntReALL) HR 2010 study, the potential of Bortezomib combined with a modified ALL relapse protocol 3 (R3) backbone as induction regimen for HR patients to improve complete 2nd remission (CR2) rates will be investigated in a randomized phase II design. Induction is followed by conventional intensive consolidation. After termination of the trial patients may be subjected to an investigational window, before all of them receive allo-HSCT.

Enrollment

250 estimated patients

Sex

All

Ages

Under 17 years old

Volunteers

No Healthy Volunteers

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 any BM relapse, early/very early isolated BM relapse, very early isolated/combined extramedullary relapse)
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

Exclusion criteria

Breakpoint cluster region-Abelson (BCR-ABL)/ t(9;22) positive ALL
Pregnancy or positive pregnancy test (urine sample positive for β-humane choriongonadotropin (HCG) > 10 U/l)
Sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 12 months 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
Objection to the study participation by a minor patient, able to object
Any patient being dependent on the investigator
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