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) or very high risk (VHR) 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.
Male or female participants between 1 and <18 years of age.
Morphologically confirmed diagnosis of first relapse HR or VHR 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). VHR first relapse is defined as relapse within 18 months of original diagnosis of ALL and/or with any of the following genetic abnormalities at original diagnosis or at relapse (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).
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.
Parallel
Inotuzumab ozogamicin
DrugInotuzumab 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
DrugThe 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)
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
Event Free Survival (EFS)
EFS will be summarized using Kaplan-Meier methods and displayed graphically by treatment arm.
Duration of Response (DoR) for Participants Who Achieved CR/CRp/CRi
DoR will be summarized using Kaplan-Meier methods.
Rate of hematopoietic stem cell transplantation (HSCT)
HSCT rate will be summarized by descriptive analyses (ie, percentage of participants who underwent HSCT after treatment).
Overall Survival (OS)
OS will be summarized by treatment arm using Kaplan-Meier methods.
