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International Study for Treatment of High Risk Childhood Relapsed ALL 2010

PHASE2RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

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Eligibility

Age eligible for study : 0 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2017-09-01

Primary completion: 2027-12-31

Study completion finish: 2027-12-31

Study type

TREATMENT

Phase

PHASE2

Trial ID

NCT03590171

Intervention or treatment

DRUG: Bortezomib

Conditions

• Acute Lymphoblastic Leukemia (ALL)

Image related to Acute Lymphoblastic Leukemia (ALL)

Condition: Acute Lymphoblastic Leukemia (ALL)
DRUG: Bortezomib
Clayton, Victoria, Australia
Sponsor: Charite University, Berlin, Germany

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Find a site

Closest Location:

Australian & New Zealand Childhood Hematology & Oncology Group

Research sites nearby

Select from list below to view details:

Australian & New Zealand Childhood Hematology & Oncology Group
Clayton, Victoria, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
NO_INTERVENTION: Arm HR-A Induction: Backbone ALL R3	Not specified
EXPERIMENTAL: Arm HR-B Induction: Backbone ALL R3 + Bortezomib	DRUG: 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.

What is the study measuring?

Primary outcome

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

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Event-free Survival	Improvement of three years event-free survival (EFS)	Year 3
Overall Survival	Improvement of three years overall survival (OS)	Year 3
Minimal Residual Disease Reduction (MRD)	Improvement of Minimal Residual Disease (MRD) reduction after induction with versus without bortezomib	Week 4
Minimal Residual Disease Load	Improvement of MRD load prior to stem cell transplantation (SCT).	Week 15
Minimal Residual Disease (MRD)	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.	Week 15
Complete Remission/Minimal Residual Disease Rates During Consolidation	Improvement of CR2 and/or MRD rates during consolidation	Week 5, 8, 11, 15
Toxicity of induction classified with the COMMON TOXICITY CRITERIA (CTC)	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).	At induction up to week 5

Frequently Asked Questions

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References

Clinical Trials Gov: International Study for Treatment of High Risk Childhood Relapsed ALL 2010