A Study to Learn More About the Study Medicine Called Inotuzumab Ozogamicin (InO) in Children (1 to <18 Years) With First Relapse ALL
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
Pfizer
100 participants
May 17, 2023
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria11
- 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.
- 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.
Exclusion Criteria7
- 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
Interventions
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.
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)
Locations(74)
View Full Details on ClinicalTrials.gov
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NCT05748171