Clinical trial NCT05748171: A Study to Learn More About the Study Medicine Called Inotuzumab Ozogamicin (InO) in Children (1 to <18 Years) With First Relapse ALL
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 FIRST RELAPSE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKAEMIA
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: ACUTE LYMPHOBLASTIC LEUKEMIA
Keywords: ALL
BCP ALL
High risk BCP ALL
Relapse ALL
Leukemia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-02-28
Enrollment: 100
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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.

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 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.

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 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).
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;
   * 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

Primary outcomes:
measure: 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)
timeFrame: After 1 treatment cycle: Day 28 +/- 2 days
Secondary outcomes:
measure: Event Free Survival (EFS)
timeFrame: 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
measure: Duration of Response (DoR) for Participants Who Achieved CR/CRp/CRi
timeFrame: 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
measure: Rate of hematopoietic stem cell transplantation (HSCT)
timeFrame: Up to 5 years from randomization
measure: Overall Survival (OS)
timeFrame: From start of treatment to date of death due to any cause: up to 5 years from randomization
measure: Number of participants reporting an Adverse Event (AE)
timeFrame: From time of informed consent up to a minimum of 60 calendar days after the last dose of study drug.
measure: Pharmacokinetics (PK) parameter: InO Cmax
timeFrame: 1 treatment cycle: 28 days
measure: Number of Adverse Events (AE) reported by severity
timeFrame: From time of informed consent up to a minimum of 60 calendar days after the last dose of study drug.
measure: Pharmacokinetics (PK) parameter: InO trough levels
timeFrame: 1 treatment cycle: 28 days
measure: Rate of Chimeric antigen receptor (CAR) T-cell therapy
timeFrame: Up to 5 years from randomisation
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: St. Anna Kinderspital
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
state: Bruxelles-capitale, Région DE
city: Gent
country: Belgium
facility: UZ Gent
state: Oost-vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams-brabant
city: Brno
country: Czechia
facility: Detska nemocnice FN Brno
state: Brno-město
city: Prague
country: Czechia
facility: Fakultni nemocnice v Motole
city: Copenhagen
country: Denmark
facility: Rigshospitalet
state: Hovedstaden
city: Helsinki
country: Finland
facility: Helsinki university hospital
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice - Hôpital l'Archet
state: Alpes-maritimes
city: Strasbourg
country: France
facility: CHU Strasbourg-Hautepierre
state: Alsace
city: Bordeaux
country: France
facility: Bordeaux University Hospital - Pellegrin
state: Aquitaine
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital des Enfants
state: Haute-garonne
city: Montpellier
country: France
facility: Hôpital Arnaud de Villeneuve - CHU Montpellier
state: Hérault
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes - Hôpital Femme-Enfant-Adolescent Chu De Nantes
state: Loire-atlantique
city: Vandoeuvre lès Nancy
country: France
facility: Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois
state: Meurthe-et-moselle
city: Lille
country: France
facility: Hôpital Jeanne de Flandre
state: Nord
city: Paris Cedex 19
country: France
facility: Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo Universita
state: Paris
city: Lyon
country: France
facility: Institut d'Hématologie et d'Oncologie Pédiatrique
city: Paris
country: France
facility: Hôpital Armand Trousseau
city: Rennes
country: France
facility: CHRU De Rennes - Hôpital Sud
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
state: Baden-württemberg
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: Baden-württemberg
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden-württemberg
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
state: Bayern
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt Goethe-Universität
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
state: Nordrhein-westfalen
city: Münster
country: Germany
facility: Universitätsklinikum Münster - Albert Schweitzer Campus
state: Nordrhein-westfalen
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein Campus Kiel
state: Schleswig-holstein
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Giessen
country: Germany
facility: Universitätsklinikum Gießen
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Központ
state: Baranya
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház
state: Borsod-abaúj-zemplén
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Petah-Tikva
country: Israel
facility: Schneider Children's Medical Center
state: Hamerkaz
city: Ramat Gan
country: Israel
facility: The Edmond and Lily Safra Children's Hospital The Chaim Sheba Medical Center Department of Pediatric
state: Hamerkaz
city: Haifa
country: Israel
facility: Rambam Health Care Campus
state: Hatsafon
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center Dana-Dwek Children's Hospital
state: Tell Abīb
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon
state: Campania
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini
state: Liguria
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
state: Lombardia
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù IRCCS
state: Roma
city: Catania
country: Italy
facility: Policlinico "G. Rodolico"
state: Sicilia
city: Padova
country: Italy
facility: Azienda Ospedale - Università Padova
state: Veneto
city: Bologna
country: Italy
facility: IRCCS - AOU di Bologna
city: Palermo
country: Italy
facility: Azienda di Rilievo Nazionale e Alta Specializzazione Civico Di Cristina Benfratelli
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Torino
country: Italy
facility: Ospedale Regina Margherita
city: Trieste
country: Italy
facility: Ospedale Infantile Burlo Garofolo
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum voor Kinderoncologie
city: Oslo
country: Norway
facility: Oslo Universitetssykehus Rikshospitalet
city: Oslo
country: Norway
facility: Radium Hospital
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
state: Dolnośląskie
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 1 im. dr. A. Jurasza w Bydgoszczy
state: Kujawsko-pomorskie
city: Bratislava
country: Slovakia
facility: Narodny ustav detskych chorob
state: Bratislavský KRAJ
city: Santiago de Compostela
country: Spain
facility: CHUS - Hospital Clinico Universitario
state: A Coruña [LA Coruña]
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [barcelona]
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Déu
state: Barcelona [barcelona]
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
state: Madrid, Comunidad DE
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Santiago de Compostela
country: Spain
facility: CHUS - Hospital Clinico Universitario
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: València
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus Lund
state: Skåne LÄN [se-12]
city: Gothenburg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset Östra
state: Västra Götalands LÄN [se-14]
city: Stockholm
country: Sweden
facility: Astrid Lindgrens Barnsjukhus
city: Bern
country: Switzerland
facility: Inselspital Bern
state: Berne
city: Lausanne
country: Switzerland
facility: CHUV (centre hospitalier universitaire vaudois)
state: Vaud
city: Zürich
country: Switzerland
facility: Kinderspital Zürich
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: