International Study for Treatment of Childhood Relapsed Precursor B-Cell ALL 2020 (IntReALL BCP 2020)

NCT07476729 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: IntReALL BCP 20202023-509392-17-00
• Study Type: interventional
• Target: 750
• Locations: 19 countries
• Sites: 19

Brief Summary

The IntReALL BCP 2020 study aims to review recent developments and findings regarding chemoimmunotherapy with inotuzumab and immunotherapy with blinatumomab and to increase the use of promising new immunotherapeutic drugs as replacements for toxic SOC chemotherapy elements. The IntReALL BCP 2020 study has the potential to improve CR and EFS rates for all SR and HR groups, as well as for patients with IEM recurrence, by replacing toxic chemotherapy with targeted, less toxic immunotherapy strategies, and could establish these new approaches as SOC for children with relapsed BCP ALL in the future.

Conditions

B-Cell Acute Lymphoblastic Leukaemia

Keywords

Lymphoblastic

Outcome Measures

Primary Outcomes (5)

• SR induction EFS

  timespan of survival until endpoint relevant event (nonresponse, death in remission, relapse, secondary malignancy) or until end of follow up

  From enrollment until 2 years after end of treatment

• SR-MRD good response consolidation DFS

  timespan of survival after achievnemt of eremission until endpoint relevant event (death in remission, relapse, secondary malignancy) or until end of follow up

  From enrollment until 2 years after end of treatment

• HR with CR2 consolidation DSF

  timespan of survival after achievnemt of eremission until endpoint relevant event (death in remission, relapse, secondary malignancy) or until end of follow up

  From enrollment until 2 years after end of treatment

• Isolated extramedullary manifestations: EFS

  timespan of survival until endpoint relevant event (nonresponse, death in remission, relapse, secondary malignancy) or until end of follow up

  From enrollment until 2 years after end of treatment

• SR induction: Pharmacokinetics Inotuzumab

  cumulative area under the concentration-time curve (AUC)

  from enrollment until day 28

Secondary Outcomes (16)

• SR induction: MRD

  Day 28 of induction

• SR-MRD good response consolidation: OS

  From enrollment until 2 years after end of treatment

• Isolated extramedullary manifestations: EFS

  From enrollment until 2 years after end of treatment

• SR induction: allo-HSCT

  week 14 to 20 after enrollment

• SR induction: OS

  from enrollment until 2 years after end of treatment

Study Arms (4)

SR induction

ACTIVE COMPARATOR

prospective, randomized 1:1, open label phase II/III trial comparing arm AI (ALLR3-MITOX) versus arm BI (InO). Randomization is stratified according to frontline treatment group (BFM, AIEOP, ALLTogether, other) and localization of relapse (BM+CNS, other)

Drug: Inotuzumab ozogamicin (INO)

SR MRD good response, consolidation

ACTIVE COMPARATOR

single arm trial with 3 courses of blinatumomab, the 1st replacing the consolidation chemotherapy element SCB2, the 2nd added on after the consolidation chemotherapy element SCB3, and the 3rd added on after the consolidation element SCB4 and 8 weeks of conventional maintenance therapy, then followed by conventional maintenance therapy being applied without reinduction chemotherapy pulses until week 132, as compared to historical controls (IntReALL BCP 2020 SR SOC induction arm compared with IntReALL SR 2010 arm B without epratuzumab)

Drug: Blinatumomab

HR with CR2, consolidation

ACTIVE COMPARATOR

single arm trial with HC1 and 1 course of blinatumomab followed by allo-HSCT compared with historical controls

Drug: Blinatumomab

Isolated extramedullary manifestations

ACTIVE COMPARATOR

single arm trial with the IntReALL SR 2010 Arm A (ALL-REZ BFM 2002) including blinatumomab replacing the chemotherapy element SCA3 compared with historical controls. SR patients will receive further conventional consolidation, local irradiation and maintenance, HR patients will be given allo-HSCT after blinatumomab

Drug: Blinatumomab

Interventions

Inotuzumab ozogamicin (INO) DRUG

Antibody Drug Conjugate (Inotuzumab)

Also known as: InO vs. R3 randomisation in SR

SR induction

Blinatumomab DRUG

Bispecific t-cell enganger BiTE

Also known as: Blinatumumab vs. historical control

HR with CR2, consolidation; Isolated extramedullary manifestations; SR MRD good response, consolidation

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• For all study questions:
• Confirmed diagnosis of 1st relapsed B-cell precursor ALL
• Patient enrolled in a participating center
• Written informed consent (IC)
• Start of treatment falling into the study period
• No participation in other clinical trials 30 days prior to study enrolment that interfere with this protocol, except trials for primary ALL
• Specific for SR induction randomization:
• Meeting SR criteria
• BM involvement (≥ 5% or ≥ 1% leukemic blasts confirmed by 2 quantitative methods)
• CD22 positive ALL (\>80% confirmed by flow-cytometry)
• No previous history of veno-occlusive disease (VOD)/ sinusoidal obstruction syndrome (SOS)
• Specific for SR MRD poor response consolidation:
• Meeting SR criteria with bone marrow involvement at relapse diagnosis
• M1/CR2 and MRD ≥ 10-4 after induction
• CD19 positive ALL at relapse (\>10%)

You may not qualify if:

• Known hypersensitivity to the active substances or excipients of the IMP's or the SOC drugs, except to PEG-asparaginase which can be replaced by Erwinase
• Left ventricular ejection fraction (LVEF) \< 50% or fractional shortening \< 25%, and/or current or prior treatment for cardiomyopathy and/or history of clinically significant arrhythmias
• Pregnancy or positive pregnancy test in female patients (urine sample positive for β-HCG \> 10 U/l) at screening or within 7 days prior to the initiation of study treatment
• Sexually active adolescents and adults not willing to use highly effective contraceptive method (pearl index \<1) until 12 months after end of anti-leukemic therapy
• Women not willing to refrain from breast feeding until 12 months after end of anti-leukemic therapy
• Relapse post allogeneic HSCT
• Relapse post chimeric antigen receptor T-cell (CAR-T) therapy
• 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
• Patients in a dependent or subordinate relationship to the investigator or site staff (e.g. employees, relatives, or students)
• No consent is given for saving and propagation of pseudonymized medical data for study reasons
• Patients with any concurrent medical condition, laboratory abnormality, concomitant treatment, or comorbidity that, in the investigator's clinical judgment would
• compromise the patient's ability to safely receive or tolerate inotuzumab ozogamicin and/or blinatumomab
• significantly interfere with assessment of treatment efficacy or safety
• make it unlikely that the patient would derive clinical benefit from protocol therapy

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (20)

St. Anna Kinderspital GmbH

Vienna, 1090, Austria

Location

Ghent University Hospital

Ghent, B-9000, Belgium

Location

Fakultni Nemocnice V Motole

Prague, 150 00, Czechia

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

HUS Helsinki University Hospital

Helsinki, FIN-00290, Finland

Location

CHU de NICE, Hôpital L'ARCHET

Nice, 06202, France

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Semmelweis University

Budapest, 1094, Hungary

Location

Tel Aviv Sourasky Medical Centre Dana-Dwek Children's Hospital

Tel Aviv, 64239, Israel

Location

Ospedale Pediatrico Bambino Gesu

Rome, 00165, Italy

Location

Prinses Máxima Centrum

Utrecht, 3584 CS, Netherlands

Location

University Wroclaw

Wroclaw, 50 354, Poland

Location

Instituto Português de Oncologia de Lisboa

Lisbon, 1099-023, Portugal

Location

Fundeni Clinical Institute, Pediatric Clinic Fundeni

Bucharest, Romania

Location

Univerzity Komenského a Národného

Bratislava, 833 40, Slovakia

Location

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

University Clinical Hospital Virgen De La Arrixaca

Murcia, 30120, Spain

Location

Karolinska University Hospital

Solna, 171 64, Sweden

Location

University Children's Hospital

Zurich, 8032, Switzerland

Location

Acıbadem University

Istanbul, 34752, Turkey (Türkiye)

Location

Related Publications (18)

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• Brivio E, Locatelli F, Lopez-Yurda M, Malone A, Diaz-de-Heredia C, Bielorai B, Rossig C, van der Velden VHJ, Ammerlaan ACJ, Thano A, van der Sluis IM, den Boer ML, Chen Y, Sleight B, Brethon B, Nysom K, Sramkova L, Ora I, Vinti L, Chen-Santel C, Zwaan CM. A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study). Blood. 2021 Mar 25;137(12):1582-1590. doi: 10.1182/blood.2020007848.

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• Wu JH, Pennesi E, Bautista F, Garrett M, Fukuhara K, Brivio E, Ammerlaan ACJ, Locatelli F, van der Sluis IM, Rossig C, Chen-Santel C, Bielorai B, Petit A, Stary J, Diaz-de-Heredia C, Rives S, O'Marcaigh A, Rizzari C, Engstler G, Nysom K, Rubio-San-Simon A, Bruno B, Bertrand Y, Brethon B, Rialland F, Plat G, Dirksen U, Sramkova L, Zwaan CM, Huitema ADR. Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059. Clin Pharmacokinet. 2024 Jul;63(7):981-997. doi: 10.1007/s40262-024-01386-z. Epub 2024 Jun 22.

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Related Links

• Project homepage

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

Inotuzumab Ozogamicin; blinatumomab

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Arend Elisabeth von Stackelberg, Dr. med., MD

  Charité - Universitätsmedizin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adriane E Napp, Dr. rer. medic, MSc

CONTACT

+17654426233; adriane.napp@charite.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med

Study Record Dates

• First Submitted: March 2, 2026
• First Posted: March 17, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2033
• Study Completion (Estimated): March 31, 2033
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); CZ (1); AU (1); HU (1); RO (1); SL (1); PL (1); DK (1); IL (1); NL (1); DE (1); FR (1); BE (1); PT (1); ES (1); TU (1); FI (1); IT (1); CH (1)