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

ACUTE LYMPHOBLASTIC LEUKEMIA Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05748171
• Other study ID #: B1931036
• Secondary ID: EU PIP Study #22
• Status: Recruiting
• Phase: Phase 2
• Start date: May 17, 2023
• Est. completion date: July 9, 2031

Study information

• Verified date: June 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: July 9, 2031
• Est. primary completion date: July 11, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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 (ie, KMT2A-rearrangements, TCF3-HLF, TCF3-PBX1, hypodiploidy, 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. 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.

Related Conditions & MeSH terms

• ACUTE LYMPHOBLASTIC LEUKEMIA
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrence

Intervention

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.
• ALLR3
The ALLR3 chemotherapy regimen (vincristine, mitoxantrone, dexamethasone, and asparaginase) has been adopted by pediatric oncology groups as treatment for pediatric relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL)

Locations

Country	Name	City	State
Austria	St. Anna Kinderspital	Vienna
Belgium	Cliniques universitaires Saint-Luc	Brussels	Bruxelles-capitale, Région DE
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	UZ Gent	Gent	Oost-vlaanderen
Belgium	UZ Leuven	Leuven	Vlaams-brabant
Czechia	Detska nemocnice FN Brno	Brno	Brno-mesto
Czechia	Fakultni nemocnice v Motole	Prague
Denmark	Rigshospitalet	Copenhagen	Hovedstaden
Finland	Helsinki university hospital	Helsinki
France	Bordeaux University Hospital - Pellegrin	Bordeaux	Aquitaine
France	Hôpital Jeanne de Flandre	Lille	Nord
France	Institut d'Hématologie et d'Oncologie Pédiatrique	Lyon
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 Universitaire de Nice - Hôpital l'Archet	Nice	Alpes-maritimes
France	Hôpital Armand Trousseau	Paris
France	Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo Universita	Paris Cedex 19	Paris
France	CHRU De Rennes - Hôpital Sud	Rennes
France	CHU Strasbourg-Hautepierre	Strasbourg	Alsace
France	CHU de Toulouse - Hôpital des Enfants	Toulouse	Haute-garonne
France	Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois	Vandoeuvre lès Nancy	Meurthe-et-moselle
Germany	Charité Campus Virchow-Klinikum	Berlin
Germany	Universitaetsklinikum Duesseldorf	Düsseldorf
Germany	Universitätsklinikum Essen	Essen	Nordrhein-westfalen
Germany	Universitätsklinikum Frankfurt Goethe-Universität	Frankfurt	Hessen
Germany	Universitaetsklinikum Freiburg	Freiburg	Baden-württemberg
Germany	Universitätsklinikum Gießen	Giessen
Germany	Universitätsklinikum Gießen	Giessen
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	Universitätsklinikum Jena	Jena
Germany	Universitaetsklinikum Schleswig-Holstein Campus Kiel	Kiel	Schleswig-holstein
Germany	Universitätsklinikum Münster - Albert Schweitzer Campus	Münster	Nordrhein-westfalen
Germany	Universitaetsklinikum Tuebingen	Tübingen	Baden-württemberg
Germany	Universitaetsklinikum Ulm	Ulm	Baden-württemberg
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg	Bayern
Greece	Aghia Sophia Children's Hospital	Athens	Attikí (region)
Hungary	Semmelweis Egyetem	Budapest
Hungary	Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház	Miskolc	Borsod-abaúj-zemplén
Hungary	Pécsi Tudományegyetem Klinikai Központ	Pécs	Baranya
Israel	Rambam Health Care Campus	Haifa	Hatsafon
Israel	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	Tel-Aviv Sourasky Medical Center Dana-Dwek Children's Hospital	Tel Aviv	Tell Abib
Italy	IRCCS - AOU di Bologna	Bologna
Italy	Policlinico "G. Rodolico"	Catania	Sicilia
Italy	IRCCS Istituto Giannina Gaslini	Genova	Liguria
Italy	Fondazione MBBM - Ematologia Pediatrica	Monza	Monza E Brianza
Italy	Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon	Napoli	Campania
Italy	Azienda Ospedale - Università Padova	Padova	Veneto
Italy	Azienda di Rilievo Nazionale e Alta Specializzazione Civico Di Cristina Benfratelli	Palermo
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Ospedale Pediatrico Bambino Gesù IRCCS	Rome	Roma
Italy	Ospedale Regina Margherita	Torino
Italy	Ospedale Infantile Burlo Garofolo	Trieste
Netherlands	Prinses Maxima Centrum voor Kinderoncologie	Utrecht
Norway	Oslo Universitetssykehus Rikshospitalet	Oslo
Norway	Radium Hospital	Oslo
Poland	Szpital Uniwersytecki nr 1 im. dr. A. Jurasza w Bydgoszczy	Bydgoszcz	Kujawsko-pomorskie
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw	Dolnoslaskie
Slovakia	Narodny ustav detskych chorob	Bratislava	Bratislavský KRAJ
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [barcelona]
Spain	Hospital Clinico Universitario Virgen de la Arrixaca	El Palmar
Spain	Hospital Sant Joan de Déu	Esplugues de Llobregat	Barcelona [barcelona]
Spain	Hospital Infantil Universitario Niño Jesús	Madrid	Madrid, Comunidad DE
Spain	Hospital Universitario La Paz	Madrid
Spain	CHUS - Hospital Clinico Universitario	Santiago de Compostela
Spain	CHUS - Hospital Clinico Universitario	Santiago de Compostela	A Coruña [LA Coruña]
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	València
Sweden	Sahlgrenska Universitetssjukhuset Östra	Gothenburg	Västra Götalands LÄN [se-14]
Sweden	Skånes Universitetssjukhus Lund	Lund	Skåne LÄN [se-12]
Sweden	Astrid Lindgrens Barnsjukhus	Stockholm
Switzerland	Inselspital Bern	Bern	Berne
Switzerland	CHUV (centre hospitalier universitaire vaudois)	Lausanne	Vaud
Switzerland	Kinderspital Zürich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Austria,  Belgium,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Netherlands,  Norway,  Poland,  Slovakia,  Spain,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	Pharmacokinetics (PK) parameter: InO Cmax	Descriptive summary statistics will be provided for InO serum concentrations at scheduled visits.	1 treatment cycle: 28 days
Secondary	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.
Secondary	Pharmacokinetics (PK) parameter: InO trough levels	Descriptive summary statistics will be provided for InO serum concentrations at scheduled visits.	1 treatment cycle: 28 days
Secondary	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

External Links

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