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AzTrials

B-Cell Acute Lymphoblastic LeukaemiaPhase 3NCT07476729

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

A Phase 3 study testing Inotuzumab ozogamicin (INO) and Blinatumomab in people with B-Cell Acute Lymphoblastic Leukaemia, run by Charite University, Berlin, Germany at 21 sites in 21 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 year and older
Conditions the study is for
B-Cell Acute Lymphoblastic Leukaemia
What is being tested?
Inotuzumab ozogamicin (INO) and Blinatumomab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
750 participants
Where
21 sitesin 21 countries
Study dates
1 Sep 2026to 31 Mar 2033
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • For all study questions:
  • Confirmed diagnosis of 1st relapsed B-cell precursor ALL
  • Patients ≥ 1 year and less than 18 years of age at diagnosis of primary ALL and less than 21 years of age at date of inclusion into the study
  • Patient enrolled in a participating center
  • Written informed consent (IC)
  • Start of treatment falling into the study period
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  • 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%)
  • Specific for SR MRD good 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%) Specific for HR consolidation arm
  • Meeting HR or VHR (in case of no possibility to be treated with CAR T cells) criteria
  • M1/CR2 after induction therapy
  • CD19 positive ALL at relapse (>10%)
  • Specific for IEM arm:
  • Histology or cytology proven extramedullary relapse
  • No bone marrow involvement (M1 at relapse diagnosis) and bone marrow MRD <1%
  • CD19 positive ALL at relapse (>10%)

Who cannot join

  • 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
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  • 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
  • preclude adherence to study procedures or follow-up requirements
  • Subjects unwilling or unable to comply with the study procedures
  • Subjects who are legally detained in an official institute
  • Specific for SR induction randomization:
  • Prior confirmed severe (grade 3 or 4) or ongoing VOD/SOS
  • Serious ongoing hepatic disease (e.g., cirrhosis, active hepatitis) not related to the current ALL relapse or current diagnostic/therapeutic measures
  • ALT > 2,5 x ULN (at relapse diagnosis before start of cytoreduction) and/or bilirubin > 1.5 x ULN
  • Patients with intolerance to PEG-asparagniase and also to Erwinase are stratified to the inotuzumab arm
  • Patients with insufficient expression of CD22 (< 80%) on leukemic blasts, they are assigned to the control chemotherapy arrm
  • Specific for blinatumomab treatment:
  • Clinically relevant CNS pathology requiring treatment (eg, unstable epilepsy)
  • Evidence of current CNS (CNS 2, CNS 3) involvement by ALL. Subjects with CNS relapse at the time of relapse are eligible if CNS is successfully treated prior to enrollment
  • Allowed systemic diseases and concomitant medication
  • Patients with Down Syndrome (DS) can be included as separate and descriptive population, not joining the study questions. Those with BM involvement receive inotuzumab ozogamicin for induction without randomization. HR patients and SR patients with MRD poor response will be allocated to allo-HSCT indication, or in case CD19 directed CAR-T-cell therapy off-protocol as individualized treatment approach. Patients with MRD good response will get the SR consolidation and maintenance therapy. Those with IEM profile will be treated according to the IEM stratum. Patients not expressing sufficiently CD22 and/or CD19 will receive the respective chemotherapy strategy.
  • Patients with BCR::ABL positive (Ph+) or BCR::ABL like (Ph-like) BCP ALL with TKI treatment option can be included as separate and descriptive population, not joining the study questions. Those with BM involvement receive inotuzumab ozogamicin plus TKI (investigators choice) without randomization for induction followed by HC1 and blinatumomab plus TKI followed by allo-HSCT. Those with IEM profile will be treated according to the IEM stratum plus TKI. Patients not expressing sufficiently CD22 and/or CD19 will receive the respective chemotherapy strategy.
  • Patients with systemic diseases such as cystic fibrosis or diabetes may be eligible for enrolment in this study only if they presumably will tolerate the protocol treatment and primary dose reductions would not be necessary.
  • Any kind of concomitant medication given due to medical reasons is allowed. Incompatibilities and drug interactions with the study medications are listed in the appendix. In case of expected adverse interactions, concomitant therapies should be changed to alternative less problematic agents if possible
  • Prohibited medication
  • Antileukemic therapy other than scheduled in the protocol (except cytoreductive pre-phase with dexamethasone)
  • Investigational drugs other than scheduled in the protocol
  • Attenuated live vaccines which are strictly prohibited during and until 6 months after end of chemotherapy or 18 months after allo-HSCT

Trial locations and contacts

21 sites in 21 countries. Contact the study team or a site near you to ask about taking part.

Adriane E Napp, Dr. rer. medic, MSc contact

+17654426233

adriane.napp@charite.de

21 sites in 21 countries

Austria1 site, 1 recruiting

  • St. Anna Kinderspital GmbH

    Vienna, 1090

    Andishe Attarbaschi, Dr. med., MD, +431401709117, andishe.attarbaschi@ccri.at

    Recruiting

Other trials in Austria

Belgium1 site, 1 recruiting

  • Ghent University Hospital

    Ghent, B-9000

    Barbara De Moerloose, Dr. med., MD

    Not yet recruiting

Other trials in Belgium

Czechia1 site, 1 recruiting

  • Fakultni Nemocnice V Motole

    Prague, 150 00

    Lucie Šrámková, Dr. med., MD, +420224436400, lucie.sramkova@fnmotol.cz

    Recruiting

Other trials in Czechia

Denmark1 site, 1 recruiting

  • Rigshospitalet

    Copenhagen, 2100

    Bodil Als-Nielsen, Dr. med., MD, +45 35451898, bodil.elise.thorhauge.als-nielsen@regionh.dk

    Recruiting

Other trials in Denmark

Finland1 site, 1 recruiting

  • HUS Helsinki University Hospital

    Helsinki, FIN-00290

    Samppa Ryhänen, Dr. med, MD, +358504270942, samppa.ryhanen@hus.fi

    Not yet recruiting

Other trials in Finland

France1 site, 1 recruiting

  • CHU de NICE, Hôpital L'ARCHET

    Nice, 06202

    Pierre Rohrlich, Dr. med., MD, +33492036377, rohrlich.ps@chu-nice.fr

    Recruiting

Other trials in France

Germany1 site, 1 recruiting

  • Charité - Universitätsmedizin Berlin

    Berlin

    Arend von Stackelberg, Dr. med., MD, +4930450666833, adriane.napp@charite.de

    Recruiting

Other trials in Germany

Hungary1 site, 1 recruiting

  • Semmelweis University

    Budapest, 1094

    Dániel Erdély, Dr. med., MD, +36 1 215 1380 ext. 52861, erdelyi.daniel@semmelweis.hu

    Not yet recruiting

Other trials in Hungary

Israel1 site, 1 recruiting

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

    Tel Aviv, 64239

    Ronit Elhasid, Dr. med., MD, +972-52-4266464, ronite@tlvmc.gov.il

    Not yet recruiting

Other trials in Israel

Italy1 site, 1 recruiting

  • Ospedale Pediatrico Bambino Gesu

    Rome, 00165

    Franco Locatelli, Dr. med., MD

    Not yet recruiting

Other trials in Italy

Netherlands1 site, 1 recruiting

  • Prinses Máxima Centrum

    Utrecht, 3584 CS

    Janine Stutterheim, Dr. med., MD, +31889727272, J.Stutterheim@prinsesmaximacentrum.nl

    Recruiting

Other trials in Netherlands

Norway1 site, 1 recruiting

  • Oslo University Hospital

    Oslo, 0424

    Jochen Büchner, Dr. med, MD, +47416023, jocbuc@ous-hf.no

    Recruiting

Other trials in Norway

Poland1 site, 1 recruiting

  • University Wroclaw

    Wroclaw, 50 354

    Monika Mielcarek, Dr. med., MD, +48 71 733 28 31, monika.mielcarek@umw.edu.pl

    Not yet recruiting

Other trials in Poland

Portugal1 site, 1 recruiting

  • Instituto Português de Oncologia de Lisboa

    Lisbon, 1099-023

    Joaquin Duarte, Dr. med., MD, +351 217229892, jduarte@ipolisboa.min-saude.pt

    Not yet recruiting

Other trials in Portugal

Romania1 site, 1 recruiting

  • Fundeni Clinical Institute, Pediatric Clinic Fundeni

    Bucharest

    Anca Colita, Dr. med., MD, +40722207268, anca.colita@umfcd.ro

    Not yet recruiting

Other trials in Romania

Slovakia1 site, 1 recruiting

  • Univerzity Komenského a Národného

    Bratislava, 833 40

    Alexandra Kolenová, Dr. med., MD, +421 (0)2 59371 230, alexandra.kolenova@nudch.eu

    Not yet recruiting

Other trials in Slovakia

Slovenia1 site, 1 recruiting

  • University Medical Centre Ljubljana

    Ljubljana, 1000

    Marko Kavčič, Dr. med., MD, +386 1 522 34 26, marko.kavcic@kclj.si

    Not yet recruiting

Other trials in Slovenia

Spain1 site, 1 recruiting

  • University Clinical Hospital Virgen De La Arrixaca

    Murcia, 30120

    José Luís Fuster Soler, Dr. med., MD, +34968369500, aaaaa@gmail.com

    Recruiting

Other trials in Spain

Sweden1 site, 1 recruiting

  • Karolinska University Hospital

    Solna, 171 64

    Petter Svenberg, Dr. med., MD, +46812380808, petter.svenberg@regionstockholm.se

    Recruiting

Other trials in Sweden

Switzerland1 site, 1 recruiting

  • University Children's Hospital

    Zurich, 8032

    Jean-Pierre Bourquin, Dr. med., MD, +41 44 249 57 16, jean-pierre.bourquin@kispi.uzh.ch

    Not yet recruiting

Other trials in Switzerland

Turkey (Türkiye)1 site, 1 recruiting

  • Acıbadem University

    Istanbul, 34752

    Koray Yalçın, Dr. med., MD, +905363236449, koray.yalcin@acibadem.com

    Not yet recruiting

Other trials in Turkey (Türkiye)

About this study

Official title: International Study for Treatment of Childhood Relapsed Precursor B-Cell ALL 2020 A Randomized Phase III Study Conducted by the Resistant Disease Committee of the International BFM Study Group

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.

Read the 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. Prognostic factors for patients with relapsed ALL are duration of first remission, immunophenotype of the malignant clone, site of relapse, molecular response to induction therapy (i.e minimal/measurable residual disease, MRD) and very high risk genetic features. The prognosis of patients with relapsed ALL was substantially improved with intensive multidrug chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the majority of patients at the cost of acute and long-term toxicity, including early and late treatment-related deaths. Patients with precursor B-cell (BCP) ALL classified as standard risk (SR) with late isolated bone marrow (BM) or combined with extramedullary (EM) disease and without high risk genetic features achieve high remission rates (> 95%) and favorable event-free survival (EFS) rates (65%) with conventional consolidation and maintenance chemotherapy if, after induction therapy, the leukemia could be reduced below the MRD level of 10-3 or 10-4, depending on the induction regimen. About 50% of SR patients experience poor MRD response after conventional chemotherapy induction and require intensified consolidation through allo-HSCT with total body irradiation to achieve EFS rates comparable to that of SR patients with good MRD response. Patients classified as high risk (HR) with early BM/EM relapse still demonstrate poor CR rates of around 65-75% being treated on standard induction therapy, and high rates of subsequent relapse. Consequently, these patients all require allo-HSCT for consolidation of 2nd remission. Patients with isolated extramedullary relapse (IEM) had a better outcome with CNS directed induction / consolidation chemotherapy as provided with the ALL-REZ BFM backbone compared to conventional induction as provided with the ALL-R3 induction. Patients with very high risk (VHR) genetic features (KMT2A::AFF1, TCF3::PBX1, TCF3::HLF rearrangements, low hypodiploidy/near haploidy, TP53 alterations) and/or very early relapses (i.e. those occurring within 18 month after initial diagnosis) have a limited benefit from conventional chemotherapy followed by allo-HSCT since their EFS rates have been reported to be below 20%.

For SR and HR patients, there is a need to replace toxic induction/consolidation chemotherapy with targeted less toxic drugs and to improve the rates of MRD negative remission after induction. In SR patients, reduction of MRD after induction could result in a lower proportion of patients with indication for allo-HSCT, a treatment that - despite being efficacious - is associated with substantial long-term sequelae. For SR patients, there is a medical need to reduce toxic consolidation and maintenance chemotherapy with targeted less toxic and potentially more effective treatment. The CD3/19 directed bi-specific monoclonal antibody blinatumomab has shown better efficacy and less toxicity compared to conventional consolidation chemotherapy in children with relapsed B-cell precursor (BCP) ALL with and without extramedullary involvement in randomized trials. The superiority of blinatumomab has been shown for HR patients before receiving HSCT in a randomized trial in Europe and for HR/IR patients before receiving HSCT and SR patients with MRD good response in a randomized trial conducted by the Children's Oncology Group. In SR patients with MRD good response, a total of 3 courses of Blinatumomab has been applied partly replacing consolidation chemotherapy and partly as add on to the standard therapy. Thus, blinatumomab can be considered as best standard of care (SOC) for early consolidation in this indication. Blinatumomab is currently being developed for subcutaneous administration. This formulation is planned to be tested in phase I/II studies in children with BCP ALL at the end of 2025. Innovative, more efficacious therapies, such as CD19-targeting CAR T cells, are urgently needed for VHR patients, since conventional therapies, including allo-HSCT, have led to dismal results.

Inotuzumab ozogamicin (InO) is a CD22 directed humanized monoclonal antibody linked to the toxin calicheamicin, belonging to the class of antibody-drug conjugate (ADC). CD22 is expressed on nearly all BCP-ALLs. After antigen binding, InO is internalized and the toxin released causing DNA damage and inducing apoptosis. InO has shown high MRD negative remission rates compared to SOC in adult and pediatric patients with relapsed/refractory BCP ALL and a safe and effective dose has been identified in a pediatric phase I/II trial.

The trial IntReALL BCP 2020 aims at integrating these recent developments and findings and at increasing the use of promising new immune-therapeutic drugs replacing toxic SOC chemotherapy elements. SR patients with bone marrow relapse will randomly receive the SOC induction ALLR3 with Mitoxantrone or InO monotherapy. Post induction, they will receive a 1st consolidation chemotherapy element (SCB1). Patients with MRD good response (< 10-4) will receive 3 courses of blinatumomab during consolidation and maintenance therapy, the 1st replacing the consolidation chemotherapy element SCB2, the 2nd added on after the 3rd consolidation chemotherapy element SCB3, and the 3rd added on after the 4rth consolidation element SCB4 and 8 weeks of conventional maintenance therapy, which, at difference of the IntReALL 2010 trial will not include vincristine/dexamethasone pulses. SR patients with MRD poor response will receive SCB1 and one blinatumomab course followed by allo-HSCT. During the course of the trial, the protocol is planned to be amended changing the blinatumomab formulation from IV to SC as soon as the latter becomes available. .

HR patients with bone marrow relapse will be included into an industry sponsored induction window trial and will join the academic IntReALL BCP 2020 study only for consolidation, since all HR patients have an indication for allo-HSCT. HR patients in CR2 after induction will receive one course of consolidation chemotherapy (HC1), one course of blinatumomab as recently established SOC followed by allo-HSCT. Whereas for the European Blina-215 trial (randomized blinatumomab versus HC3) 2 courses HC1 and HC2 were given as standard early consolidation, in the COG trial (AALL1331) the whole consolidation chemotherapy has been replaced by blinatumomab. One standard chemotherapy consolidation course HC1 is considered as feasible compromise and provides time for B-cell regeneration after InO as prerequisite for T-cell expansion during the blinatumomab consolidation course.

Patients with IEM will receive the IntReALL SR2010 arm A backbone with blinatumomab replacing the chemotherapy element SCA3 as bridge to allo-HSCT in those with early relapse or to further consolidation therapy in those with late relapse.

The hypotheses addressed within the IntReALL BCP 2020 trial are, that:

  1. EFS-probability in SR patients will be improved in the InO arm leading to higher CR rates, better MRD response and to less patients requiring allo-HSCT compared to standard of care induction chemotherapy ALL R3 in a prospective randomized trial.
  2. SR patients with MRD good response will have a better DFS probability 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, followed by maintenance therapy until week 132, being applied without vincristine/dexamethasone pulses, as compared to historical controls. Blinatumomab given subcutaneously is planned to be investigated accordingly after finalization of the recruitment for the IV trial within a planned amendment of the study.
  3. HR patients with CR2 after induction will have a non-inferior DFS with HC1 and blinatumomab compared to historical controls with HC1, HC2 and blinatumomab.
  4. EFS probability in patients with IEM relapse will be improved and toxicity will be reduced with blinatumomab as late consolidation element compared to historical controls (ALL-REZ BFM 2002).

The IntReALL BCP 2020 trial has the potential to improve CR and EFS rates for all SR and HR groups, as well as in patients with IEM relapse, by replacing toxic chemotherapy with targeted less toxic immunotherapy strategies and may establish these new approaches as SOC for children with relapsed BCP ALL in future. In addition, the IntReALL BCP 2020 trial has the ambition to reduce the proportion of SR patients in need of an allograft for consolidation therapy.

Being tested
Inotuzumab ozogamicin (INO), Blinatumomab
Keywords
Lymphoblastic
Medical subject headings
Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Inotuzumab ozogamicin (INO)Drug

    Also called InO vs. R3 randomisation in SR

    Antibody Drug Conjugate (Inotuzumab)

  • BlinatumomabDrug

    Also called Blinatumumab vs. historical control

    Bispecific t-cell enganger BiTE

Study groups in NCT07476729
Study groupRoleWhat they receive
SR inductionActive comparatorprospective, 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)
Receives: Drug: Inotuzumab ozogamicin (INO)
SR MRD good response, consolidationActive comparatorsingle 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)
Receives: Drug: Blinatumomab
HR with CR2, consolidationActive comparatorsingle arm trial with HC1 and 1 course of blinatumomab followed by allo-HSCT compared with historical controls
Receives: Drug: Blinatumomab
Isolated extramedullary manifestationsActive comparatorsingle 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
Receives: Drug: Blinatumomab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. SR induction EFS

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

    Measured: From enrollment until 2 years after end of treatment

  2. 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

    Measured: From enrollment until 2 years after end of treatment

  3. 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

    Measured: From enrollment until 2 years after end of treatment

  4. Isolated extramedullary manifestations: EFS

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

    Measured: From enrollment until 2 years after end of treatment

  5. SR induction: Pharmacokinetics Inotuzumab

    cumulative area under the concentration-time curve (AUC)

    Measured: from enrollment until day 28

Secondary outcomes (16)

  1. SR induction: MRD

    MRD negativity rate after induction quantified by flow- and/or PCR techniques

    Measured: Day 28 of induction

  2. SR-MRD good response consolidation: OS

    timespan of survival until death or until end of follow up

    Measured: From enrollment until 2 years after end of treatment

  3. Isolated extramedullary manifestations: EFS

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

    Measured: From enrollment until 2 years after end of treatment

  4. SR induction: allo-HSCT

    Proportion of patients requiring allo-HSCT

    Measured: week 14 to 20 after enrollment

  5. SR induction: OS

    timespan of survival until death or until end of follow up

    Measured: from enrollment until 2 years after end of treatment

  6. SR induction: Toxicity

    Toxicity (assessed by CTCAE grades and SAE reports)

    Measured: from enrollement until end of protocol therapy

  7. SR induction: CD19 positive cells

    Rate of patients with CD19 positive cells after SCB1 prior to Blinatumomab

    Measured: week 9 after enrollment

  8. SR-MRD good response consolidation: Toxicity

    Toxicity (quantified by CTCAE grades and SAE reports)

    Measured: from enrollment until end of treatment (week 132)

  9. Isolated extramedullary manifestations: OS

    timespan of survival until death or until end of follow up

    Measured: from enrollment until 2 years after end of treatment

  10. Isolated extramedullary manifestations: DFS by MRD

    timespan of survival after achievnemt of eremission until endpoint relevant event (death in remission, relapse, secondary malignancy) or until end of follow up by MD after induction (cut-off 10-4)

    Measured: from enrollment until 2 years after end of treatment

  11. HR with CR2 consolidation: OS

    timespan of survival until death or until end of follow up

    Measured: from enrollment until 2 years after end of treatment

  12. HR with CR2 consolidation: Toxicity

    Toxicity (assessed by CTCAE grades and SAE reports)

    Measured: from enrollment until end of treatment (day 100 post HSCT)

  13. HR with CR2 consolidation: MRD

    MRD negativity rates before allo-HSCT quantified by flow- and/or PCR techniques

    Measured: week 13 after enrollment

  14. HR with CR2 consolidation: allo-HSCT

    allo-HSCT rates

    Measured: week 14 after enrollment

  15. Inotuzumab PK

    Maximum and through concentrations of inotuzumab

    Measured: from enrollment until end of induction (day 28), before and 1 hour after start of inotuzumab infusion

  16. Inotuzumab PK exposure response relationship

    CR- and MRD negativity rates by inotuzumab AUC

    Measured: from enrollment until end of induction (day 28)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2026
  2. Study start1 Sep 2026
  3. Primary completion31 Mar 2033 (estimated)
  4. Study completion31 Mar 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
750 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07476729
Sponsor's protocol ID
IntReALL BCP 2020
Other IDs
2023-509392-17-00, 2023
Status last verified
Oct 2026
First submitted
2 Mar 2026
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Eckert C, Parker C, Moorman AV, Irving JA, Kirschner-Schwabe R, Groeneveld-Krentz S, Revesz T, Hoogerbrugge P, Hancock J, Sutton R, Henze G, Chen-Santel C, Attarbaschi A, Bourquin JP, Sramkova L, Zimmermann M, Krishnan S, von Stackelberg A, Saha V. Risk factors and outcomes in children with high-risk B-cell precursor and T-cell relapsed acute lymphoblastic leukaemia: combined analysis of ALLR3 and ALL-REZ BFM 2002 clinical trials. Eur J Cancer. 2021 Jul;151:175-189. doi: 10.1016/j.ejca.2021.03.034. Epub 2021 May 16.

    PubMed 34010787

  • Hagedorn N, Acquaviva C, Fronkova E, von Stackelberg A, Barth A, zur Stadt U, Schrauder A, Trka J, Gaspar N, Seeger K, Henze G, Cave H, Eckert C; Resistant Disease Committee of the International BFM study group. Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of "isolated" and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group. Blood. 2007 Dec 1;110(12):4022-9. doi: 10.1182/blood-2007-04-082040. Epub 2007 Aug 24.

    PubMed 17720883

  • Eckert C, Henze G, Seeger K, Hagedorn N, Mann G, Panzer-Grumayer R, Peters C, Klingebiel T, Borkhardt A, Schrappe M, Schrauder A, Escherich G, Sramkova L, Niggli F, Hitzler J, von Stackelberg A. Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group. J Clin Oncol. 2013 Jul 20;31(21):2736-42. doi: 10.1200/JCO.2012.48.5680. Epub 2013 Jun 17.

    PubMed 23775972

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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Inotuzumab ozogamicin (INO) and Blinatumomab in people with B-Cell Acute Lymphoblastic Leukaemia, run by Charite University, Berlin, Germany at 21 sites in 21 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Austria, Belgium, Czechia, Denmark, Finland and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Adriane E Napp, Dr. rer. medic, MSc (+17654426233, adriane.napp@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

SR induction EFS (time frame: From enrollment until 2 years after end of treatment). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07476729, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

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