A Study to Learn More About the Study Medicine Called Inotuzumab Ozogamicin (InO) in Children (1 to <18 Years) With First Relapse ALL
- Conditions
- ACUTE LYMPHOBLASTIC LEUKEMIA
- Interventions
- Drug: ALLR3
- Registration Number
- NCT05748171
- Lead Sponsor
- Pfizer
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
-
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.
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
- 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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Inotuzumab ozogamicin 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 ALLR3 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
- Primary Outcome Measures
Name Time Method 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 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
- Secondary Outcome Measures
Name Time Method Rate of hematopoietic stem cell transplantation (HSCT) Up to 5 years from randomization HSCT rate will be summarized by descriptive analyses (ie, percentage of participants who underwent HSCT after treatment).
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. 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.
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 EFS will be summarized using Kaplan-Meier methods and displayed graphically by treatment arm.
Rate of Chimeric antigen receptor (CAR) T-cell therapy Up to 5 years from randomisation 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).
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 DoR will be summarized using Kaplan-Meier methods.
Pharmacokinetics (PK) parameter: InO Cmax 1 treatment cycle: 28 days Descriptive summary statistics will be provided for InO serum concentrations at scheduled visits.
Number of Adverse Events (AE) reported by severity From time of informed consent up to a minimum of 60 calendar days after the last dose of study drug. AEs will be graded by the investigator according to the CTCAE (Common Terminology Criteria for Adverse Events) version 4.03.
Overall Survival (OS) From start of treatment to date of death due to any cause: up to 5 years from randomization OS will be summarized by treatment arm using Kaplan-Meier methods.
Pharmacokinetics (PK) parameter: InO trough levels 1 treatment cycle: 28 days Descriptive summary statistics will be provided for InO serum concentrations at scheduled visits.
Trial Locations
- Locations (72)
St. Anna Kinderspital
🇦🇹Vienna, Austria
Helsinki university hospital
🇫🇮Helsinki, Finland
Cliniques universitaires Saint-Luc
🇧🇪Brussels, Bruxelles-capitale, Région DE, Belgium
UZ Gent
🇧🇪Gent, Oost-vlaanderen, Belgium
UZ Leuven
🇧🇪Leuven, Vlaams-brabant, Belgium
Detska nemocnice FN Brno
🇨🇿Brno, Brno-město, Czechia
Fakultni nemocnice v Motole
🇨🇿Prague, Czechia
Rigshospitalet
🇩🇰Copenhagen, Hovedstaden, Denmark
Centre Hospitalier Universitaire de Nice - Hôpital l'Archet
🇫🇷Nice, Alpes-maritimes, France
CHU Strasbourg-Hautepierre
🇫🇷Strasbourg, Alsace, France
Bordeaux University Hospital - Pellegrin
🇫🇷Bordeaux, Aquitaine, France
CHU de Toulouse - Hôpital des Enfants
🇫🇷Toulouse, Haute-garonne, France
Hôpital Arnaud de Villeneuve - CHU Montpellier
🇫🇷Montpellier, Hérault, France
Centre Hospitalier Universitaire de Nantes - Hôpital Femme-Enfant-Adolescent Chu De Nantes
🇫🇷Nantes, Loire-atlantique, France
Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois
🇫🇷Vandoeuvre lès Nancy, Meurthe-et-moselle, France
Hôpital Jeanne de Flandre
🇫🇷Lille, Nord, France
Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo Universita
🇫🇷Paris Cedex 19, Paris, France
Institut d'Hématologie et d'Oncologie Pédiatrique
🇫🇷Lyon, France
Hôpital Armand Trousseau
🇫🇷Paris, France
CHRU De Rennes - Hôpital Sud
🇫🇷Rennes, France
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Baden-württemberg, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tübingen, Baden-württemberg, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Baden-württemberg, Germany
Universitaetsklinikum Wuerzburg
🇩🇪Wuerzburg, Bayern, Germany
Universitätsklinikum Frankfurt Goethe-Universität
🇩🇪Frankfurt, Hessen, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Nordrhein-westfalen, Germany
Universitätsklinikum Münster - Albert Schweitzer Campus
🇩🇪Münster, Nordrhein-westfalen, Germany
Universitaetsklinikum Schleswig-Holstein Campus Kiel
🇩🇪Kiel, Schleswig-holstein, Germany
Charité Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Universitaetsklinikum Duesseldorf
🇩🇪Düsseldorf, Germany
Universitätsklinikum Gießen
🇩🇪Giessen, Germany
Universitaetsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Jena
🇩🇪Jena, Germany
Pécsi Tudományegyetem Klinikai Központ
🇭🇺Pécs, Baranya, Hungary
Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház
🇭🇺Miskolc, Borsod-abaúj-zemplén, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Schneider Children's Medical Center
🇮🇱Petah-Tikva, Hamerkaz, Israel
The Edmond and Lily Safra Children's Hospital The Chaim Sheba Medical Center Department of Pediatric
🇮🇱Ramat Gan, Hamerkaz, Israel
Rambam Health Care Campus
🇮🇱Haifa, Hatsafon, Israel
Tel-Aviv Sourasky Medical Center Dana-Dwek Children's Hospital
🇮🇱Tel Aviv, Tell Abīb, Israel
Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon
🇮🇹Napoli, Campania, Italy
IRCCS Istituto Giannina Gaslini
🇮🇹Genova, Liguria, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, Lombardia, Italy
Ospedale Pediatrico Bambino Gesù IRCCS
🇮🇹Rome, Roma, Italy
Policlinico "G. Rodolico"
🇮🇹Catania, Sicilia, Italy
Azienda Ospedale - Università Padova
🇮🇹Padova, Veneto, Italy
IRCCS - AOU di Bologna
🇮🇹Bologna, Italy
Azienda di Rilievo Nazionale e Alta Specializzazione Civico Di Cristina Benfratelli
🇮🇹Palermo, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Ospedale Regina Margherita
🇮🇹Torino, Italy
Ospedale Infantile Burlo Garofolo
🇮🇹Trieste, Italy
Prinses Maxima Centrum voor Kinderoncologie
🇳🇱Utrecht, Netherlands
Oslo Universitetssykehus Rikshospitalet
🇳🇴Oslo, Norway
Radium Hospital
🇳🇴Oslo, Norway
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
🇵🇱Wrocław, Dolnośląskie, Poland
Szpital Uniwersytecki nr 1 im. dr. A. Jurasza w Bydgoszczy
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
Narodny ustav detskych chorob
🇸🇰Bratislava, Bratislavský KRAJ, Slovakia
CHUS - Hospital Clinico Universitario
🇪🇸Santiago de Compostela, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [barcelona], Spain
Hospital Sant Joan de Déu
🇪🇸Esplugues de Llobregat, Barcelona [barcelona], Spain
Hospital Infantil Universitario Niño Jesús
🇪🇸Madrid, Madrid, Comunidad DE, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
🇪🇸El Palmar, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸València, Spain
Skånes Universitetssjukhus Lund
🇸🇪Lund, Skåne LÄN [se-12], Sweden
Sahlgrenska Universitetssjukhuset Östra
🇸🇪Gothenburg, Västra Götalands LÄN [se-14], Sweden
Astrid Lindgrens Barnsjukhus
🇸🇪Stockholm, Sweden
Inselspital Bern
🇨🇭Bern, Berne, Switzerland
CHUV (centre hospitalier universitaire vaudois)
🇨🇭Lausanne, Vaud, Switzerland
Kinderspital Zürich
🇨🇭Zürich, Switzerland