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JOURNAL ONKOLOGIE – STUDIE

International Study for Treatment of High Risk Childhood Relapsed ALL 2010

Rekrutierend

NCT-Nummer:
NCT03590171

Studienbeginn:
September 2017

Letztes Update:
09.02.2024

Wirkstoff:
Bortezomib

Indikation (Clinical Trials):
Precursor Cell Lymphoblastic Leukemia-Lymphoma

Geschlecht:
Alle

Altersgruppe:
Kinder (0-17)

Phase:
Phase 2

Sponsor:
Charite University, Berlin, Germany

Collaborator:
Australian & New Zealand Children's Haematology/Oncology Group, St. Anna Kinderkrebsforschung, CCRI (co-sponsor, Austria), European Organisation for Research and Treatment of Cancer - EORTC, University Hospital Motol (Co-Sponsor Czech Republic), Copenhagen Un

Studienleiter

Arend von Stackelberg, MD
Principal Investigator
Charite University, Berlin, Germany

Kontakt

Arend von Stackelberg, MD
Kontakt:
Phone: +49(0)30-450666
Phone (ext.): 833
E-Mail: arend.stackelberg@charite.de» Kontaktdaten anzeigen

Studienlocations
(3 von 15)

Alle anzeigen

Studien-Informationen

Detailed 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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Rate of Complete Remission (Time Frame - Week 4):
Rate of complete second remission (CR2) quantified by cytology after induction with standard chemotherapy + bortezomib (arm B) compared with standard chemotherapy (arm A).



Secondary outcome:

1. Event-free Survival (Time Frame - Year 3):
Improvement of three years event-free survival (EFS)

2. Overall Survival (Time Frame - Year 3):
Improvement of three years overall survival (OS)

3. Minimal Residual Disease Reduction (MRD) (Time Frame - Week 4):
Improvement of Minimal Residual Disease (MRD) reduction after induction with versus without bortezomib

4. Minimal Residual Disease Load (Time Frame - Week 15):
Improvement of MRD load prior to stem cell transplantation (SCT).

5. Minimal Residual Disease (MRD) (Time Frame - Week 15):
Prognostic relevance of MRD pre stem cell transplantation (SCT). MRD will be quantified before stem cell transplantation with polymerase chain reaction (PCR) and will be related to EFS after SCT. Multicolour flow cytometry will be used in parallel with PCR. Flow cytometry is used instead of PCR if PCR based MRD-quantification cannot be performed, because criteria for a reliable and reproducible sensitive quantification are not fulfilled.

6. Complete Remission/Minimal Residual Disease Rates During Consolidation (Time Frame - Week 5, 8, 11, 15):
Improvement of CR2 and/or MRD rates during consolidation

7. Toxicity of induction classified with the COMMON TOXICITY CRITERIA (CTC) (Time Frame - At induction up to week 5):
Toxicity of induction with versus without bortezomib. Toxicity of the central nervous system and peripheral neuropathy will be classified with the COMMON TOXICITY CRITERIA (CTC).

Studien-Arme

  • No Intervention: Arm HR-A
    Induction: Backbone ALL R3
  • Experimental: Arm HR-B
    Induction: Backbone ALL R3 + Bortezomib

Geprüfte Regime

  • Bortezomib:
    Patients randomised to the HR-B arm receive induction, consolidation with the modified ALL R3 protocol. In this arm, patients are randomized to receive Bortezomib together with the ALL R3 protocol during induction. Administration of Bortezomib: 1.3 mg/m2 as intravenous bolus or subcutaneously (SC, at the discretion of the treating physician) on days 1 and 4 of weeks 1 and 3.

Quelle: ClinicalTrials.gov


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