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

NCT05748171 · Pfizer
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Official title
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
About this study
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.
Eligibility criteria
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 design
Enrollment target: 100 participants
Allocation: randomized
Masking: none
Age groups: child
Timeline
Starts: 2023-05-17
Estimated completion: 2036-05-25
Last updated: 2026-07-09
Interventions
Drug: Inotuzumab ozogamicinDrug: ALLR3
Primary outcomes
  • 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) (After 1 treatment cycle: Day 28 +/- 2 days)
Sponsor
Pfizer · industry
Contacts & investigators
ContactPfizer CT.gov Call Center · contact · ClinicalTrials.gov_Inquiries@pfizer.com · 1-800-718-1021
InvestigatorPfizer CT.gov Call Center · study_director, Pfizer
All locations (68)
St. Anna KinderspitalRecruiting
Vienna, Austria
Cliniques universitaires Saint-LucRecruiting
Brussels, Bruxelles-capitale, Région de, Belgium
UZ GentRecruiting
Ghent, Oost-vlaanderen, Belgium
UZ LeuvenRecruiting
Leuven, Vlaams-brabant, Belgium
Detska nemocnice FN BrnoRecruiting
Brno, Brno-město, Czechia
Fakultni Nemocnice Motol a HomolkaRecruiting
Prague, Czechia
RigshospitaletRecruiting
Copenhagen, Capital Region, Denmark
Helsinki university hospitalRecruiting
Helsinki, Finland
Centre Hospitalier Universitaire de Nice - Hôpital l'ArchetRecruiting
Nice, Alpes-maritimes, France
CHU Strasbourg-Hautepierre, Service d'hematologie oncologie pediatrique, pediatrie 3Recruiting
Strasbourg, Alsace, France
Bordeaux University Hospital - PellegrinRecruiting
Bordeaux, Aquitaine, France
CHU de Toulouse - Hôpital des Enfants - Hemato-Immuno-OncologieRecruiting
Toulouse, Haute-garonne, France
Hôpital Arnaud de Villeneuve - CHU MontpellierRecruiting
Montpellier, Hérault, France
Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de BraboisRecruiting
Vandœuvre-lès-Nancy, Meurthe-et-moselle, France
Hôpital Jeanne de Flandre - CHRURecruiting
Lille, NORD, France
Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo UniversitaRecruiting
Paris, Paris, France
Institut d'Hématologie et d'Oncologie PédiatriqueRecruiting
Lyon, France
CHU de Nantes - Hôpital Mère - EnfantsRecruiting
Nantes, France
Hôpital Armand TrousseauRecruiting
Paris, France
CHRU De Rennes - Hôpital SudRecruiting
Rennes, France
Universitaetsklinikum FreiburgRecruiting
Freiburg im Breisgau, Baden-Wurttemberg, Germany
Universitaetsklinikum UlmRecruiting
Ulm, Baden-Wurttemberg, Germany
Universitaetsklinikum WuerzburgRecruiting
Würzburg, Bavaria, Germany
Universitätsklinikum Frankfurt Goethe-UniversitätRecruiting
Frankfurt am Main, Hesse, Germany
Medizinische Hochschule HannoverRecruiting
Hanover, Lower Saxony, Germany
Universitaetsklinikum EssenRecruiting
Essen, North Rhine-Westphalia, Germany
Universitätsklinikum Münster - Albert Schweitzer CampusRecruiting
Münster, North Rhine-Westphalia, Germany
Universitaetsklinikum Schleswig-Holstein Campus KielRecruiting
Kiel, Schleswig-Holstein, Germany
Charité Campus Virchow-KlinikumRecruiting
Berlin, Germany
Universitaetsklinikum DuesseldorfRecruiting
Düsseldorf, Germany
Universitätsklinikum GießenRecruiting
Giessen, Germany
Universitaetsklinikum Hamburg-EppendorfRecruiting
Hamburg, Germany
Medizinische Hochschule HannoverRecruiting
Hanover, Germany
Universitätsklinikum JenaRecruiting
Jena, Germany
Schneider Children's Medical CenterRecruiting
Petah Tikva, Central District, Israel
The Edmond and Lily Safra Children's Hospital; The Chaim Sheba Medical CenterRecruiting
Ramat Gan, Central District, Israel
Rambam Health Care CampusRecruiting
Haifa, Northern District, Israel
Tel-Aviv Sourasky Medical Center Dana-Dwek Children's HospitalRecruiting
Tel Aviv, TELL ABĪB, Israel
Azienda Ospedaliera di Rilievo Nazional Santobono PausiliponRecruiting
Naples, Campania, Italy
IRCCS Istituto Giannina GasliniRecruiting
Genoa, Liguria, Italy
Fondazione IRCCS San Gerardo dei TintoriRecruiting
Monza, Lombardy, Italy
Ospedale Pediatrico Bambino Gesù IRCCSRecruiting
Rome, ROMA, Italy
Policlinico "G. Rodolico"Recruiting
Catania, Sicily, Italy
Azienda Ospedale - Università PadovaRecruiting
Padova, Veneto, Italy
Fondazione IRCCS Policlinico San MatteoRecruiting
Pavia, Italy
Ospedale Regina MargheritaRecruiting
Torino, Italy
IRCCS Materno Infantile Burlo GarofoloRecruiting
Trieste, Italy
Prinses Maxima Centrum voor KinderoncologieRecruiting
Utrecht, Netherlands
Oslo Universitetssykehus RikshospitaletRecruiting
Oslo, Norway
Radium HospitalRecruiting
Oslo, Norway
Szpital Uniwersytecki nr 1 im. dr. A. Jurasza w BydgoszczyRecruiting
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we WrocławiuRecruiting
Wroclaw, Lower Silesian Voivodeship, Poland
Narodny ustav detskych chorobRecruiting
Bratislava, Bratislava Region, Slovakia
CHUS - Hospital Clinico UniversitarioRecruiting
Santiago de Compostela, A Coruña [LA Coruña], Spain
Hospital Universitari Vall d'HebronRecruiting
Barcelona, Barcelona [barcelona], Spain
Hospital Sant Joan de DéuRecruiting
Esplugues de Llobregat, Barcelona [barcelona], Spain
Hospital Infantil Universitario Niño JesúsRecruiting
Madrid, Madrid, Comunidad de, Spain
Hospital Clinico Universitario Virgen de la ArrixacaRecruiting
El Palmar, Murcia, Spain
Hospital Universitario La PazRecruiting
Madrid, Spain
CHUS - Hospital Clinico UniversitarioRecruiting
Santiago de Compostela, Spain
Hospital Universitario Virgen Del RocioRecruiting
Seville, Spain
Hospital Universitari i Politecnic La FeRecruiting
Valencia, Spain
Skånes Universitetssjukhus LundRecruiting
Lund, Skåne LÄN [se-12], Sweden
Sahlgrenska Universitetssjukhuset ÖstraRecruiting
Gothenburg, Västra Götalands LÄN [se-14], Sweden
Astrid Lindgrens BarnsjukhusRecruiting
Stockholm, Sweden
Inselspital BernRecruiting
Bern, Canton of Bern, Switzerland
CHUV (centre hospitalier universitaire vaudois)Recruiting
Lausanne, Canton of Vaud, Switzerland
Kinderspital ZürichRecruiting
Zurich, Switzerland
A Study to Learn More About the Study Medicine Called Inotuzumab Ozogamicin (InO) in Children (1 to <18 Years) With First Relapse ALL · TrialPath