Trial Title:
A Study to Learn More About the Study Medicine Called Inotuzumab Ozogamicin (InO) in Children (1 to <18 Years) With First Relapse ALL
NCT ID:
NCT05748171
Condition:
ACUTE LYMPHOBLASTIC LEUKEMIA
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Recurrence
Inotuzumab Ozogamicin
Conditions: Keywords:
ALL
BCP ALL
High risk BCP ALL
Relapse ALL
Leukemia
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
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
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Inotuzumab ozogamicin
Description:
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.
Arm group label:
Inotuzumab ozogamicin
Other name:
Besponsa
Intervention type:
Drug
Intervention name:
ALLR3
Description:
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)
Arm group label:
ALLR3
Other name:
R3
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.
Criteria for 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
Gender:
All
Minimum age:
1 Year
Maximum age:
17 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
St. Anna Kinderspital
Address:
City:
Vienna
Zip:
1090
Country:
Austria
Status:
Recruiting
Facility:
Name:
Cliniques universitaires Saint-Luc
Address:
City:
Brussels
Zip:
1200
Country:
Belgium
Status:
Recruiting
Facility:
Name:
UZ Gent
Address:
City:
Gent
Zip:
9000
Country:
Belgium
Status:
Recruiting
Facility:
Name:
UZ Leuven
Address:
City:
Leuven
Zip:
3000
Country:
Belgium
Status:
Recruiting
Facility:
Name:
Cliniques Universitaires Saint-Luc
Address:
City:
Brussels
Zip:
1200
Country:
Belgium
Status:
Recruiting
Facility:
Name:
Detska nemocnice FN Brno
Address:
City:
Brno
Zip:
613 00
Country:
Czechia
Status:
Recruiting
Facility:
Name:
Fakultni nemocnice v Motole
Address:
City:
Prague
Zip:
150 06
Country:
Czechia
Status:
Recruiting
Facility:
Name:
Rigshospitalet
Address:
City:
Copenhagen
Zip:
DK-2100
Country:
Denmark
Status:
Recruiting
Facility:
Name:
Helsinki university hospital
Address:
City:
Helsinki
Zip:
00290
Country:
Finland
Status:
Recruiting
Facility:
Name:
Centre Hospitalier Universitaire de Nice - Hôpital l'Archet
Address:
City:
Nice
Zip:
06202
Country:
France
Status:
Recruiting
Facility:
Name:
CHU Strasbourg-Hautepierre
Address:
City:
Strasbourg
Zip:
67098
Country:
France
Status:
Recruiting
Facility:
Name:
Bordeaux University Hospital - Pellegrin
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Status:
Recruiting
Facility:
Name:
CHU de Toulouse - Hôpital des Enfants
Address:
City:
Toulouse
Zip:
31059
Country:
France
Status:
Recruiting
Facility:
Name:
Hôpital Arnaud de Villeneuve - CHU Montpellier
Address:
City:
Montpellier
Zip:
34090
Country:
France
Status:
Recruiting
Facility:
Name:
Centre Hospitalier Universitaire de Nantes - Hôpital Femme-Enfant-Adolescent Chu De Nantes
Address:
City:
Nantes
Zip:
44000
Country:
France
Status:
Recruiting
Facility:
Name:
Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois
Address:
City:
Vandoeuvre lès Nancy
Zip:
54511
Country:
France
Status:
Recruiting
Facility:
Name:
Hôpital Jeanne de Flandre
Address:
City:
Lille
Zip:
59037
Country:
France
Status:
Recruiting
Facility:
Name:
Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo Universita
Address:
City:
Paris Cedex 19
Zip:
75935
Country:
France
Status:
Recruiting
Facility:
Name:
Institut d'Hématologie et d'Oncologie Pédiatrique
Address:
City:
Lyon
Zip:
69008
Country:
France
Status:
Recruiting
Facility:
Name:
Hôpital Armand Trousseau
Address:
City:
Paris
Zip:
75571
Country:
France
Status:
Recruiting
Facility:
Name:
CHRU De Rennes - Hôpital Sud
Address:
City:
Rennes
Zip:
35203
Country:
France
Status:
Recruiting
Facility:
Name:
Universitaetsklinikum Freiburg
Address:
City:
Freiburg
Zip:
79106
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitaetsklinikum Tuebingen
Address:
City:
Tübingen
Zip:
72076
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitaetsklinikum Ulm
Address:
City:
Ulm
Zip:
89081
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitaetsklinikum Wuerzburg
Address:
City:
Wuerzburg
Zip:
97080
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitätsklinikum Frankfurt Goethe-Universität
Address:
City:
Frankfurt
Zip:
60590
Country:
Germany
Status:
Recruiting
Facility:
Name:
Medizinische Hochschule Hannover
Address:
City:
Hannover
Zip:
30625
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitätsklinikum Essen
Address:
City:
Essen
Zip:
45122
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitätsklinikum Münster - Albert Schweitzer Campus
Address:
City:
Münster
Zip:
48149
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitaetsklinikum Schleswig-Holstein Campus Kiel
Address:
City:
Kiel
Zip:
24105
Country:
Germany
Status:
Recruiting
Facility:
Name:
Charité Campus Virchow-Klinikum
Address:
City:
Berlin
Zip:
13353
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitaetsklinikum Duesseldorf
Address:
City:
Düsseldorf
Zip:
40225
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitätsklinikum Gießen
Address:
City:
Giessen
Zip:
35392
Country:
Germany
Status:
Not yet recruiting
Facility:
Name:
Universitätsklinikum Gießen
Address:
City:
Giessen
Zip:
35392
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitaetsklinikum Hamburg-Eppendorf
Address:
City:
Hamburg
Zip:
20246
Country:
Germany
Status:
Recruiting
Facility:
Name:
Medizinische Hochschule Hannover
Address:
City:
Hannover
Zip:
30625
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitätsklinikum Jena
Address:
City:
Jena
Zip:
07747
Country:
Germany
Status:
Recruiting
Facility:
Name:
Aghia Sophia Children's Hospital
Address:
City:
Athens
Zip:
115 27
Country:
Greece
Status:
Not yet recruiting
Facility:
Name:
Pécsi Tudományegyetem Klinikai Központ
Address:
City:
Pécs
Zip:
7623
Country:
Hungary
Status:
Recruiting
Facility:
Name:
Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház
Address:
City:
Miskolc
Zip:
3526
Country:
Hungary
Status:
Recruiting
Facility:
Name:
Semmelweis Egyetem
Address:
City:
Budapest
Zip:
1094
Country:
Hungary
Status:
Recruiting
Facility:
Name:
Schneider Children's Medical Center
Address:
City:
Petah-Tikva
Zip:
49202
Country:
Israel
Status:
Recruiting
Facility:
Name:
The Edmond and Lily Safra Children's Hospital The Chaim Sheba Medical Center Department of Pediatric
Address:
City:
Ramat Gan
Zip:
5265601
Country:
Israel
Status:
Recruiting
Facility:
Name:
Rambam Health Care Campus
Address:
City:
Haifa
Zip:
3109601
Country:
Israel
Status:
Recruiting
Facility:
Name:
Tel-Aviv Sourasky Medical Center Dana-Dwek Children's Hospital
Address:
City:
Tel Aviv
Zip:
6423906
Country:
Israel
Status:
Recruiting
Facility:
Name:
Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon
Address:
City:
Napoli
Zip:
80123
Country:
Italy
Status:
Recruiting
Facility:
Name:
IRCCS Istituto Giannina Gaslini
Address:
City:
Genova
Zip:
16147
Country:
Italy
Status:
Recruiting
Facility:
Name:
Fondazione MBBM - Ematologia Pediatrica
Address:
City:
Monza
Zip:
20900
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ospedale Pediatrico Bambino Gesù IRCCS
Address:
City:
Rome
Zip:
00165
Country:
Italy
Status:
Recruiting
Facility:
Name:
Policlinico "G. Rodolico"
Address:
City:
Catania
Zip:
95123
Country:
Italy
Status:
Recruiting
Facility:
Name:
Azienda Ospedale - Università Padova
Address:
City:
Padova
Zip:
35128
Country:
Italy
Status:
Recruiting
Facility:
Name:
IRCCS - AOU di Bologna
Address:
City:
Bologna
Zip:
40138
Country:
Italy
Status:
Recruiting
Facility:
Name:
Azienda di Rilievo Nazionale e Alta Specializzazione Civico Di Cristina Benfratelli
Address:
City:
Palermo
Zip:
90127
Country:
Italy
Status:
Recruiting
Facility:
Name:
Fondazione IRCCS Policlinico San Matteo
Address:
City:
Pavia
Zip:
27100
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ospedale Regina Margherita
Address:
City:
Torino
Zip:
10126
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ospedale Infantile Burlo Garofolo
Address:
City:
Trieste
Zip:
34137
Country:
Italy
Status:
Recruiting
Facility:
Name:
Prinses Maxima Centrum voor Kinderoncologie
Address:
City:
Utrecht
Zip:
3584 CS
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
Oslo Universitetssykehus Rikshospitalet
Address:
City:
Oslo
Zip:
0372
Country:
Norway
Status:
Recruiting
Facility:
Name:
Radium Hospital
Address:
City:
Oslo
Zip:
0379
Country:
Norway
Status:
Recruiting
Facility:
Name:
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
Address:
City:
Wrocław
Zip:
50-556
Country:
Poland
Status:
Recruiting
Facility:
Name:
Szpital Uniwersytecki nr 1 im. dr. A. Jurasza w Bydgoszczy
Address:
City:
Bydgoszcz
Zip:
85-094
Country:
Poland
Status:
Recruiting
Facility:
Name:
Narodny ustav detskych chorob
Address:
City:
Bratislava
Zip:
833 40
Country:
Slovakia
Status:
Recruiting
Facility:
Name:
CHUS - Hospital Clinico Universitario
Address:
City:
Santiago de Compostela
Zip:
15706
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitari Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Sant Joan de Déu
Address:
City:
Esplugues de Llobregat
Zip:
08950
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Infantil Universitario Niño Jesús
Address:
City:
Madrid
Zip:
28009
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Clinico Universitario Virgen de la Arrixaca
Address:
City:
El Palmar
Zip:
30120
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario La Paz
Address:
City:
Madrid
Zip:
28046
Country:
Spain
Status:
Recruiting
Facility:
Name:
CHUS - Hospital Clinico Universitario
Address:
City:
Santiago de Compostela
Zip:
15706
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario Virgen Del Rocio
Address:
City:
Sevilla
Zip:
41013
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitari i Politecnic La Fe
Address:
City:
València
Zip:
46026
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Skånes Universitetssjukhus Lund
Address:
City:
Lund
Zip:
22185
Country:
Sweden
Status:
Recruiting
Facility:
Name:
Sahlgrenska Universitetssjukhuset Östra
Address:
City:
Gothenburg
Zip:
416 85
Country:
Sweden
Status:
Recruiting
Facility:
Name:
Astrid Lindgrens Barnsjukhus
Address:
City:
Stockholm
Zip:
17067
Country:
Sweden
Status:
Recruiting
Facility:
Name:
Inselspital Bern
Address:
City:
Bern
Zip:
3010
Country:
Switzerland
Status:
Recruiting
Facility:
Name:
CHUV (centre hospitalier universitaire vaudois)
Address:
City:
Lausanne
Zip:
1011
Country:
Switzerland
Status:
Recruiting
Facility:
Name:
Kinderspital Zürich
Address:
City:
Zürich
Zip:
8032
Country:
Switzerland
Status:
Recruiting
Start date:
May 17, 2023
Completion date:
July 9, 2031
Lead sponsor:
Agency:
Pfizer
Agency class:
Industry
Source:
Pfizer
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05748171
https://pmiform.com/clinical-trial-info-request?StudyID=B1931036
