A Study to Learn More About the Study Medicine Called Inotuzumab Ozogamicin (InO) in Children (1 to <18 Years) With First Relapse ALL

A PROSPECTIVE, RANDOMIZED, OPEN-LABEL PHASE 2 STUDY TO EVALUATE THE SUPERIORITY OF INOTUZUMAB OZOGAMICIN MONOTHERAPY VERSUS ALLR3 FOR INDUCTION TREATMENT OF CHILDHOOD HIGH-RISK OR VERY HIGH-RISK FIRST RELAPSE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKAEMIA

This prospective, randomized, multicenter, open-label Phase 2 study is designed to evaluate the superiority of InO monotherapy vs ALLR3 after 1 cycle of induction treatment in paediatric participants (between 1 and <18 years) with High Risk (HR) or very high risk (VHR) first bone marrow relapse CD22-positive BCP ALL, and to evaluate the safety and tolerability, PK and long-term efficacy. Treatment with study intervention will end after induction therapy; follow-up will continue for up to 5 years from randomization.

Study Overview

• Status: Recruiting
• Conditions: ACUTE LYMPHOBLASTIC LEUKEMIA
• Intervention / Treatment: Drug: Inotuzumab ozogamicin; Drug: ALLR3

Detailed Description

This prospective, randomized, multicenter, open-label, Phase 2 study is designed to evaluate the superiority of InO monotherapy vs ALLR3, after 1 cycle of induction treatment in paediatric participants (between 1 and <18 years) with HR or VHR first bone marrow relapse CD22-positive BCP ALL, and to evaluate the safety and tolerability, PK and long-term efficacy. Treatment with study intervention will end after induction therapy; follow-up for efficacy and safety will continue for up to 5 years from randomization.

End of Treatment is defined as occurring upon recovery from 1 cycle of study therapy (Day 28 ± 2 days), or one day before initiation of new anticancer therapy, whichever occurs first.

Approximately 100 participants will be randomized (2:1) to receive 1 cycle of either InO monotherapy or ALLR3 (block 1) therapy during induction. Two interim analyses (approximately 50% and 75% enrollment) fort the primary outcome measure followed by a final analysis are planned to assess efficacy and futility (non-binding).

After completion of induction therapy (ie, study therapy), it is anticipated that the majority of responding participants will proceed immediately to consolidation therapy. Non-responders are expected to proceed with salvage therapy at the investigator's discretion. Participants responding to induction therapy are expected to proceed to SOC consolidation therapy upon recovery of blood counts, but no sooner than 7 days after last dose of study intervention.

All participants (responders and non-responders) will proceed to long-term follow-up for this study. All subsequent anticancer therapy will be determined by the treating physician.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • St. Anna Kinderspital
• Belgium
  • Bruxelles-capitale, Région de
    • Brussels, Bruxelles-capitale, Région de, Belgium, 1200
      • Recruiting
      • Cliniques Universitaires Saint-Luc
  • Oost-vlaanderen
    • Ghent, Oost-vlaanderen, Belgium, 9000
      • Recruiting
      • UZ Gent
  • Vlaams-brabant
    • Leuven, Vlaams-brabant, Belgium, 3000
      • Recruiting
      • UZ Leuven
• Czechia
  • Prague, Czechia, 150 00
    • Recruiting
    • Fakultni Nemocnice Motol a Homolka
  • Brno-město
    • Brno, Brno-město, Czechia, 613 00
      • Recruiting
      • Detska nemocnice FN Brno
• Denmark
  • Capital Region
    • Copenhagen, Capital Region, Denmark, DK-2100
      • Recruiting
      • Rigshospitalet
• Finland
  • Helsinki, Finland, 00290
    • Recruiting
    • Helsinki University Hospital
• France
  • Lyon, France, 69008
    • Recruiting
    • Institut d'Hématologie et d'Oncologie Pédiatrique
  • Nantes, France, 44000
    • Recruiting
    • CHU de Nantes - Hôpital Mère - Enfants
  • Paris, France, 75571
    • Recruiting
    • Hôpital Armand Trousseau
  • Rennes, France, 35203
    • Recruiting
    • CHRU De Rennes - Hôpital Sud
  • Alpes-maritimes
    • Nice, Alpes-maritimes, France, 06202
      • Recruiting
      • Centre Hospitalier Universitaire de Nice - Hôpital l'Archet
  • Alsace
    • Strasbourg, Alsace, France, 67000
      • Recruiting
      • CHU Strasbourg-Hautepierre, Service d'hematologie oncologie pediatrique, pediatrie 3
  • Aquitaine
    • Bordeaux, Aquitaine, France, 33076
      • Recruiting
      • Bordeaux University Hospital - Pellegrin
  • Haute-garonne
    • Toulouse, Haute-garonne, France, 31059
      • Recruiting
      • CHU de Toulouse - Hôpital des Enfants - Hemato-Immuno-Oncologie
  • Hérault
    • Montpellier, Hérault, France, 34090
      • Recruiting
      • Hôpital Arnaud de Villeneuve - CHU Montpellier
  • Meurthe-et-moselle
    • Vandœuvre-lès-Nancy, Meurthe-et-moselle, France, 54511
      • Recruiting
      • Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois
  • NORD
    • Lille, NORD, France, 59037
      • Recruiting
      • Hôpital Jeanne de Flandre - CHRU
  • Paris
    • Paris, Paris, France, 75935
      • Recruiting
      • Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo Universita
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charité Campus Virchow-Klinikum
  • Düsseldorf, Germany, 40225
    • Recruiting
    • Universitaetsklinikum Duesseldorf
  • Giessen, Germany, 35392
    • Recruiting
    • Universitätsklinikum Gießen
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitaetsklinikum Hamburg-Eppendorf
  • Hanover, Germany, 30625
    • Recruiting
    • Medizinische Hochschule Hannover
  • Jena, Germany, 07747
    • Recruiting
    • Universitatsklinikum Jena
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Recruiting
      • Universitaetsklinikum Freiburg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Recruiting
      • Universitaetsklinikum Tuebingen
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Recruiting
      • Universitaetsklinikum Ulm
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Recruiting
      • Universitaetsklinikum Wuerzburg
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Recruiting
      • Universitätsklinikum Frankfurt Goethe-Universität
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Recruiting
      • Medizinische Hochschule Hannover
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45122
      • Recruiting
      • Universitaetsklinikum Essen
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Recruiting
      • Universitätsklinikum Münster - Albert Schweitzer Campus
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Recruiting
      • Universitaetsklinikum Schleswig-Holstein Campus Kiel
• Hungary
  • Budapest, Hungary, 1094
    • Recruiting
    • Semmelweis Egyetem
  • Baranya
    • Pécs, Baranya, Hungary, 7623
      • Recruiting
      • Pecsi Tudomanyegyetem Klinikai Kozpont
• India
  • Delhi, India, 110085
    • Not yet recruiting
    • Rajiv Gandhi Cancer Institute and Research Centre
  • Haryana
    • Gurugram, Haryana, India, 122001
      • Not yet recruiting
      • Medanta - The Medicity
• Israel
  • Central District
    • Petah Tikva, Central District, Israel, 49202
      • Recruiting
      • Schneider Children's Medical Center
    • Ramat Gan, Central District, Israel, 5265601
      • Recruiting
      • The Edmond and Lily Safra Children's Hospital; The Chaim Sheba Medical Center
  • Northern District
    • Haifa, Northern District, Israel, 3109601
      • Recruiting
      • Rambam Health Care Campus
  • TELL ABĪB
    • Tel Aviv, TELL ABĪB, Israel, 6423906
      • Recruiting
      • Tel-Aviv Sourasky Medical Center Dana-Dwek Children's Hospital
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS - AOU di Bologna
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione IRCCS Policlinico San Matteo
  • Torino, Italy, 10126
    • Recruiting
    • Ospedale Regina Margherita
  • Trieste, Italy, 34137
    • Recruiting
    • IRCCS Materno Infantile Burlo Garofolo
  • Campania
    • Naples, Campania, Italy, 80123
      • Recruiting
      • Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon
  • Liguria
    • Genoa, Liguria, Italy, 16147
      • Recruiting
      • IRCCS Istituto Giannina Gaslini
  • Lombardy
    • Monza, Lombardy, Italy, 20900
      • Recruiting
      • Fondazione IRCCS San Gerardo dei Tintori
  • ROMA
    • Rome, ROMA, Italy, 00165
      • Recruiting
      • Ospedale Pediatrico Bambino Gesù IRCCS
  • Sicily
    • Catania, Sicily, Italy, 95123
      • Recruiting
      • Policlinico "G. Rodolico"
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Recruiting
      • Azienda Ospedale - Università Padova
• Netherlands
  • Utrecht, Netherlands, 3584 CS
    • Recruiting
    • Prinses Maxima Centrum voor Kinderoncologie
• Norway
  • Oslo, Norway, 0372
    • Recruiting
    • Oslo Universitetssykehus Rikshospitalet
  • Oslo, Norway, 0379
    • Recruiting
    • Radium Hospital
• Poland
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-094
      • Recruiting
      • Szpital Uniwersytecki nr 1 im. dr. A. Jurasza w Bydgoszczy
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 50-556
      • Recruiting
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
• Slovakia
  • Bratislava Region
    • Bratislava, Bratislava Region, Slovakia, 833 40
      • Recruiting
      • Narodny ustav detskych chorob
• Spain
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Santiago de Compostela, Spain, 15706
    • Recruiting
    • CHUS - Hospital Clinico Universitario
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitari i Politecnic La Fe
  • A Coruña [LA Coruña]
    • Santiago de Compostela, A Coruña [LA Coruña], Spain, 15706
      • Recruiting
      • CHUS - Hospital Clinico Universitario
  • Barcelona [barcelona]
    • Barcelona, Barcelona [barcelona], Spain, 08035
      • Recruiting
      • Hospital Universitari Vall d'Hebron
    • Esplugues de Llobregat, Barcelona [barcelona], Spain, 08950
      • Recruiting
      • Hospital Sant Joan de Déu
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28009
      • Recruiting
      • Hospital Infantil Universitario Nino Jesus
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Hospital Clínico Universitario Virgen de la Arrixaca
• Sweden
  • Stockholm, Sweden, 17067
    • Recruiting
    • Astrid Lindgrens Barnsjukhus
  • Skåne LÄN [se-12]
    • Lund, Skåne LÄN [se-12], Sweden, 22185
      • Recruiting
      • Skånes Universitetssjukhus Lund
  • Västra Götalands LÄN [se-14]
    • Gothenburg, Västra Götalands LÄN [se-14], Sweden, 416 85
      • Recruiting
      • Sahlgrenska Universitetssjukhuset Östra
• Switzerland
  • Zurich, Switzerland, 8008
    • Recruiting
    • Kinderspital Zürich
  • Canton of Bern
    • Bern, Canton of Bern, Switzerland, 3010
      • Recruiting
      • Inselspital Bern
  • Canton of Vaud
    • Lausanne, Canton of Vaud, Switzerland, 1011
      • Recruiting
      • CHUV (centre hospitalier universitaire vaudois)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female participants between 1 and <18 years of age.

2. Morphologically confirmed diagnosis of first relapse HR or VHR BCP ALL; HR first relapse is defined as relapse occurring within 18 to 30 months of original diagnosis of ALL or within 6 months of completion of primary therapy, and lacking any identified very high-risk genetic abnormalities (Groeneveld-Krentz et al, 2019) (ie, KMT2A::AFF1 fusion [t(4;11)(q21;q23)], TCF3-HLF fusion [t(17;19)(q22;p13)], TCF3-PBX1 fusion [t(1;19)(q23;p13.3)], hypodiploidy [<40 chromosomes] or masked low hypodiploidy (Molina et al, 2021), TP53 alteration). VHR first relapse is defined as relapse within 18 months of original diagnosis of ALL and/or with any of the following genetic abnormalities at original diagnosis or at relapse (Groeneveld-Krentz et al, 2019) (ie, KMT2A::AFF1 fusion [t(4;11)(q21;q23)], TCF3-HLF fusion [t(17;19)(q22;p13)], TCF3-PBX1 fusion [t(1;19)(q23;p13.3)], hypodiploidy [<40 chromosomes] or masked low hypodiploidy (Molina et al, 2021), TP53 alteration).

   • CD22-positive ALL as defined by local institution;
   • Bone marrow involvement of ≥ 5% leukemic blasts (≥ M2 status).

3. Adequate serum chemistry parameters:

   • An eGFR in participants 1 to <2 years of age, or eCrCl in those 2 to <18 years of age, ≥30 mL/min using the recommended formula in Section 10.10.2.
   • AST and ALT ≤5 × institutional ULN at the time of randomization or pre-cytoreduction/general anesthesia; (Refer to Appendix 9 for France-specific requirement on the ALT/AST threshold);
   • Total bilirubin ≤1.5 × institutional ULN unless the participant has documented Gilbert's syndrome;
4. Prior history of thrombosis during corticosteroid use and/or asparaginase are eligible provided the patient receives anti-coagulant prophylaxis per institutional guidelines.
5. Cardiac shortening fraction ≥ 30% by echocardiogram or ejection fraction >50% by MUGA.

6 Participants with combined bone marrow and testicular relapse are eligible assuming orchiectomy is performed prior to randomization or is planned at the end of induction therapy.

5.2. Exclusion Criteria

1. Any history of prior or ongoing hepatic SOS or prior liver failure [defined as severe acute liver injury with encephalopathy and impaired synthetic function (INR of ≥1.5)].
2. Prior allo-HSCT or CAR T-cell therapy.
3. Isolated extramedullary leukemia.
4. Philadelphia-chromosome positive ALL, ie. BCR-ABL/t(9;22) present.
5. Prior therapy with a calicheamicin-conjugated antibody (eg, InO or gemtuzumab ozogamicin).
6. Participants with active, uncontrolled bacterial, fungal, or viral infection.
7. Hypersensitivity/allergy to both PEG-ASP and Erwinia-ASP

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inotuzumab ozogamicin; Each participant in the InO arm will receive 1 course (3 doses) of InO, as follows: Day 1: 0.8 mg/m2; Days 8 (±1 day) and Day 15 (±1 day): 0.5 mg/m2/dose	Drug: Inotuzumab ozogamicin; Inotuzumab ozogamicin (BESPONSA™) is a CD22 targeted antibody drug conjugate (ADC) approved in several countries for the treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). The approved starting dose is 1.8mg/m2/cycle.; Other Names: Besponsa
Active Comparator: ALLR3; Mitoxantrone 10 mg/m2 on Days 1 and 2 Vincristine 1.5 mg/m2 (max single dose 2 mg) administered on Days 3, 10, 17 and 24 Dexamethasone 20 mg/m2/day administered orally (or IV) divided into two daily doses (maximum 40 mg/day) as two 5-day blocks on Days 1-5 and Days 15-19. PEG-asparaginase 1000 units/m2 IV administered on Days 3 and 17. In case of hypersensitivity/allergic reaction to PEG-asparaginase, each dose of PEG-asparaginase will be replaced by Erwinia-asparaginase at a dose of 20,000 units/m² IV or IM every other day for a total of 6 doses	Drug: ALLR3; The ALLR3 chemotherapy regimen (vincristine, mitoxantrone, dexamethasone, and PEG-asparaginase [or erwinia-asparaginase in the event of an allergic reaction to PEG-asparaginase]) has been adopted by pediatric oncology groups as treatment for pediatric relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL); Other Names: R3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum Residual Disease (MRD) Negativity in participants achieving complete response (CR), complete response with incomplete platelet count recovery (CRp), or complete response with incomplete count recovery (CRi)	MRD negativity status is determined based on the minimum MRD percentage between the date of CR/CRp/CRi and end of treatment test as assessed by RQ-PCR, with reflex to FC result if MRD is non-evaluable by RQ-PCR	After 1 treatment cycle: Day 28 +/- 2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival (EFS)	EFS will be summarized using Kaplan-Meier methods and displayed graphically by treatment arm.	From study start to first event (progression, relapse, failure to achieve CR/CRp/CRi by the end of induction, MRD persistence prior to HSCT [hematopoietic stem cell transplant], second malignancy, or death): up to 5 years from randomization
Duration of Response (DoR) for Participants Who Achieved CR/CRp/CRi	DoR will be summarized using Kaplan-Meier methods.	From date of first response to date of first event (objective progression, relapse as determined by investigator assessment, MRD persistence prior to HSCT, or death due to any cause, whichever occurs first): up to 5 years from End of Treatment
Rate of hematopoietic stem cell transplantation (HSCT)	HSCT rate will be summarized by descriptive analyses (ie, percentage of participants who underwent HSCT after treatment).	Up to 5 years from randomization
Overall Survival (OS)	OS will be summarized by treatment arm using Kaplan-Meier methods.	From start of treatment to date of death due to any cause: up to 5 years from randomization
Number of participants reporting an Adverse Event (AE)	The number and percentage of participants who experienced any AE, SAE (Serious Adverse Event), treatment related AE, and treatment related SAE will be summarized according to worst toxicity grades.	From time of informed consent up to a minimum of 60 calendar days after the last dose of study drug.
Pharmacokinetics (PK) parameter: InO Cmax	Descriptive summary statistics will be provided for InO serum concentrations at scheduled visits.	1 treatment cycle: 28 days
Number of Adverse Events (AE) reported by severity	AEs will be graded by the investigator according to the CTCAE (Common Terminology Criteria for Adverse Events) version 4.03.	From time of informed consent up to a minimum of 60 calendar days after the last dose of study drug.
Pharmacokinetics (PK) parameter: InO trough levels	Descriptive summary statistics will be provided for InO serum concentrations at scheduled visits.	1 treatment cycle: 28 days
Rate of Chimeric antigen receptor (CAR) T-cell therapy	CAR T-cell therapy rate will be summarized by descriptive analyses (ie, the number, percent of participants who underwent CAR T-cell therapy after treatment).	Up to 5 years from randomisation

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2023
• Primary Completion (Estimated): October 31, 2033
• Study Completion (Estimated): November 4, 2036

Study Registration Dates

• First Submitted: January 20, 2023
• First Submitted That Met QC Criteria: February 17, 2023
• First Posted (Actual): February 28, 2023

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: ALL; Leukemia; BCP ALL; High risk BCP ALL; Relapse ALL; Very high risk BCP ALL
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Hemic and Lymphatic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Amino Acids, Peptides, and Proteins; Proteins; Carbohydrates; Glycosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Aminoglycosides; Calicheamicins; Inotuzumab Ozogamicin
• Other Study ID Numbers: B1931036; 2023-509810-13-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No