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

NCT05748171 | Recruiting Phase 2 DMC

• 2 other identifiers: B19310362023-509810-13-00
• Study Type: interventional
• Target: 100
• Locations: 18 countries
• Sites: 76

Brief Summary

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) 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.

Conditions

ACUTE LYMPHOBLASTIC LEUKEMIA

Keywords

ALL; BCP ALL; High risk BCP ALL; Relapse ALL; Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Event Free Survival (EFS)

  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

  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)

  Up to 5 years from randomization

• Overall Survival (OS)

  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)

  From time of informed consent up to a minimum of 60 calendar days after the last dose of study drug.

Study Arms (2)

Inotuzumab ozogamicin

EXPERIMENTAL

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

ALLR3

ACTIVE COMPARATOR

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

Interventions

Inotuzumab ozogamicin DRUG

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.

Also known as: Besponsa

Inotuzumab ozogamicin

ALLR3 DRUG

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)

Also known as: R3

ALLR3

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female participants between 1 and \<18 years of age.
• Morphologically confirmed diagnosis of first relapse HR 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).
• CD22-positive ALL as defined by local institution;
• Bone marrow involvement of ≥ 5% leukemic blasts (≥ M2 status).
• 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;
• Total bilirubin ≤1.5 × institutional ULN unless the participant has documented Gilbert's syndrome;
• Prior history of thrombosis during corticosteroid use and/or asparaginase are eligible provided the patient receives anti-coagulant prophylaxis per institutional guidelines.
• Cardiac shortening fraction ≥ 30% by echocardiogram or ejection fraction \>50% by MUGA.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (76)

St. Anna Kinderspital

Vienna, 1090, Austria

RECRUITING

Cliniques universitaires Saint-Luc

Brussels, Bruxelles-capitale, Région de, 1200, Belgium

RECRUITING

UZ Gent

Ghent, Oost-vlaanderen, 9000, Belgium

RECRUITING

UZ Leuven

Leuven, Vlaams-brabant, 3000, Belgium

RECRUITING

Detska nemocnice FN Brno

Brno, Brno-město, 613 00, Czechia

RECRUITING

Fakultni Nemocnice Motol a Homolka

Prague, 150 00, Czechia

RECRUITING

Rigshospitalet

Copenhagen, Capital Region, DK-2100, Denmark

RECRUITING

Helsinki university hospital

Helsinki, 00290, Finland

RECRUITING

Centre Hospitalier Universitaire de Nice - Hôpital l'Archet

Nice, Alpes-maritimes, 06202, France

RECRUITING

CHU Strasbourg-Hautepierre, Service d'hematologie oncologie pediatrique, pediatrie 3

Strasbourg, Alsace, 67000, France

RECRUITING

Bordeaux University Hospital - Pellegrin

Bordeaux, Aquitaine, 33076, France

RECRUITING

CHU de Toulouse - Hôpital des Enfants - Hemato-Immuno-Oncologie

Toulouse, Haute-garonne, 31059, France

RECRUITING

Hôpital Arnaud de Villeneuve - CHU Montpellier

Montpellier, Hérault, 34090, France

RECRUITING

Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois

Vandœuvre-lès-Nancy, Meurthe-et-moselle, 54511, France

RECRUITING

Hôpital Jeanne de Flandre - CHRU

Lille, NORD, 59037, France

RECRUITING

Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo Universita

Paris, Paris, 75935, France

RECRUITING

Institut d'Hématologie et d'Oncologie Pédiatrique

Lyon, 69008, France

RECRUITING

CHU de Nantes - Hôpital Mère - Enfants

Nantes, 44000, France

RECRUITING

Hôpital Armand Trousseau

Paris, 75571, France

RECRUITING

CHRU De Rennes - Hôpital Sud

Rennes, 35203, France

RECRUITING

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

RECRUITING

Universitaetsklinikum Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Universitaetsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

RECRUITING

Universitaetsklinikum Wuerzburg

Würzburg, Bavaria, 97080, Germany

RECRUITING

Universitätsklinikum Frankfurt Goethe-Universität

Frankfurt am Main, Hesse, 60590, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

RECRUITING

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, 45122, Germany

RECRUITING

Universitätsklinikum Münster - Albert Schweitzer Campus

Münster, North Rhine-Westphalia, 48149, Germany

RECRUITING

Universitaetsklinikum Schleswig-Holstein Campus Kiel

Kiel, Schleswig-Holstein, 24105, Germany

RECRUITING

Charité Campus Virchow-Klinikum

Berlin, 13353, Germany

RECRUITING

Universitaetsklinikum Duesseldorf

Düsseldorf, 40225, Germany

RECRUITING

Universitätsklinikum Gießen

Giessen, 35392, Germany

RECRUITING

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, 30625, Germany

RECRUITING

Universitätsklinikum Jena

Jena, 07747, Germany

RECRUITING

Pécsi Tudományegyetem Klinikai Központ

Pécs, Baranya, 7623, Hungary

RECRUITING

Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház

Miskolc, Borsod-Abauj Zemplen county, 3526, Hungary

RECRUITING

Semmelweis Egyetem

Budapest, 1094, Hungary

RECRUITING

Medanta - The Medicity

Gurugram, Haryana, 122001, India

NOT YET RECRUITING

Rajiv Gandhi Cancer Institute and Research Centre

Delhi, 110085, India

NOT YET RECRUITING

Schneider Children's Medical Center

Petah Tikva, Central District, 49202, Israel

RECRUITING

The Edmond and Lily Safra Children's Hospital; The Chaim Sheba Medical Center

Ramat Gan, Central District, 5265601, Israel

RECRUITING

Rambam Health Care Campus

Haifa, Northern District, 3109601, Israel

RECRUITING

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

Tel Aviv, TELL ABĪB, 6423906, Israel

RECRUITING

Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon

Naples, Campania, 80123, Italy

RECRUITING

IRCCS Istituto Giannina Gaslini

Genoa, Liguria, 16147, Italy

RECRUITING

Fondazione IRCCS San Gerardo dei Tintori

Monza, Lombardy, 20900, Italy

RECRUITING

Ospedale Pediatrico Bambino Gesù IRCCS

Rome, ROMA, 00165, Italy

RECRUITING

Policlinico "G. Rodolico"

Catania, Sicily, 95123, Italy

RECRUITING

Azienda Ospedale - Università Padova

Padova, Veneto, 35128, Italy

RECRUITING

IRCCS - AOU di Bologna

Bologna, 40138, Italy

RECRUITING

Azienda di Rilievo Nazionale e Alta Specializzazione Civico Di Cristina Benfratelli

Palermo, 90127, Italy

RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

RECRUITING

Ospedale Regina Margherita

Torino, 10126, Italy

RECRUITING

IRCCS Materno Infantile Burlo Garofolo

Trieste, 34137, Italy

RECRUITING

Prinses Maxima Centrum voor Kinderoncologie

Utrecht, 3584 CS, Netherlands

RECRUITING

Oslo Universitetssykehus Rikshospitalet

Oslo, 0372, Norway

RECRUITING

Radium Hospital

Oslo, 0379, Norway

RECRUITING

Szpital Uniwersytecki nr 1 im. dr. A. Jurasza w Bydgoszczy

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-094, Poland

RECRUITING

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu

Wroclaw, Lower Silesian Voivodeship, 50-556, Poland

RECRUITING

Narodny ustav detskych chorob

Bratislava, Bratislava Region, 833 40, Slovakia

RECRUITING

CHUS - Hospital Clinico Universitario

Santiago de Compostela, A Coruña [LA Coruña], 15706, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [barcelona], 08035, Spain

RECRUITING

Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcelona [barcelona], 08950, Spain

RECRUITING

Hospital Infantil Universitario Niño Jesús

Madrid, Madrid, Comunidad de, 28009, Spain

RECRUITING

Hospital Clinico Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

CHUS - Hospital Clinico Universitario

Santiago de Compostela, 15706, Spain

RECRUITING

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

RECRUITING

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

RECRUITING

Skånes Universitetssjukhus Lund

Lund, Skåne LÄN [se-12], 22185, Sweden

RECRUITING

Sahlgrenska Universitetssjukhuset Östra

Gothenburg, Västra Götalands LÄN [se-14], 416 85, Sweden

RECRUITING

Astrid Lindgrens Barnsjukhus

Stockholm, 17067, Sweden

RECRUITING

Inselspital Bern

Bern, Canton of Bern, 3010, Switzerland

RECRUITING

CHUV (centre hospitalier universitaire vaudois)

Lausanne, Canton of Vaud, 1011, Switzerland

RECRUITING

Kinderspital Zürich

Zurich, 8008, Switzerland

RECRUITING

Related Links

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

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Interventions

Inotuzumab Ozogamicin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; 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

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Central Study Contacts

Pfizer CT.gov Call Center

CONTACT

1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized at 2:1 ratio, so that approximately 67 participants will receive InO and 33 participants will receive the comparator treatment regimen, ALLR3

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: February 28, 2023
• Study Start: May 17, 2023
• Primary Completion (Estimated): October 31, 2033
• Study Completion (Estimated): November 4, 2036
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

PL (2); AU (1); CH (3); DE (15); IL (4); IN (2); SL (1); DK (1); FR (12); FI (1); IT (11); SE (3); BE (3); ES (9); CZ (2); NL (1); NO (2); HU (3)