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

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 - InO Monotherapy vs ALLR3 as Induction Treatment of childhood ALL

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON53624

Enrollment

Registered

2022-11-08

Start date

2023-07-31

Completion date

Unknown

Last updated

2024-09-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Relapsed Acute Lymphoblastic Leukemia and Relapsed Childhood leukemia

Interventions

Intervention Groups and Duration Participants will be randomized (2:1) to receive 1 cycle of either InO monotherapy or ALLR3 (block 1) therapy during induction. InO Monotherapy Arm Participant in th

Eligibility

Age

No minimum to 17 Years

Inclusion criteria

Inclusion criteria: Participants must meet the following key inclusion criteria to be eligible for enrollment into the study: 1. Male or female participants between 1 and = 5% leukemic blasts (>= M2 status). 3. Cardiac shortening fraction >= 30% by echocardiogram or ejection fraction > 50% by MUGA.

Exclusion criteria

Exclusion criteria: Participants with any of the following key characteristics/conditions will be excluded: 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.

Design outcomes

Primary

Measure	Time frame
Primary: Efficacy: To demonstrate the superiority of InO monotherapy vs ALLR3 induction in paediatric participants between 1 and	—

Secondary

Measure	Time frame
Secondary: Key Secondary Efficacy: To evaluate the long-term efficacy of InO monotherapy vs ALLR3 regimen with respect to EFS Endpoints: EFS, defined as the time from randomization until objective progression, relapse from CR/CRp/CRi, based on investigator assessment per response criteria, failure to achieve CR/CRp/CRi by the end of induction, MRD persistence prior to HSCT, second malignancy, or death due to any cause. Key Secondary Estimand: EFS: treatment effect in the targeted population of InO monotherapy induction on EFS based on investigator assessment compared to the ALLR3 induction from randomization to the date of event. Efficacy: To evaluate the long-term efficacy of InO monotherapy vs ALLR3 regimen with respect to: • DOR • HSCT rate • CAR T-cell therapy rate • OS Endpoints: DOR, defined as time from date of first documented response (CR/CRp/CRi) to the date of first documented objective progression, relapse from CR/CRp/CRi as determined by investigator assessment per modified NCCN response criteria, MRD persistence prior to HSCT, or death due to any cause, whichever occurs first. HSCT (and CAR T-cell therapy) rate, defined as the number and percentage of participants being transplanted and those receiving CAR T-cell therapy after treatment with InO or ALLR3. OS, defined as the time from the date of randomization to the date of death due to any cause. Estimands: Not Applicable Safety: To evaluate the safety and tolerability of InO monotherapy vs ALLR3 induction Enpoints: Incidence and severity of AEs graded per NCI CTCAE v4.03. Estimands: Not Applicable Pharmacokinetics To evaluate the PK of InO npoints:Cmax and Ctrough Estimands: Not Applicable	—

Measure

Time frame

Secondary: Key Secondary Efficacy: To evaluate the long-term efficacy of InO monotherapy vs ALLR3 regimen with respect to EFS Endpoints: EFS, defined as the time from randomization until objective progression, relapse from CR/CRp/CRi, based on investigator assessment per response criteria, failure to achieve CR/CRp/CRi by the end of induction, MRD persistence prior to HSCT, second malignancy, or death due to any cause. Key Secondary Estimand: EFS: treatment effect in the targeted population of InO monotherapy induction on EFS based on investigator assessment compared to the ALLR3 induction from randomization to the date of event. Efficacy: To evaluate the long-term efficacy of InO monotherapy vs ALLR3 regimen with respect to: • DOR • HSCT rate • CAR T-cell therapy rate • OS Endpoints: DOR, defined as time from date of first documented response (CR/CRp/CRi) to the date of first documented objective progression, relapse from CR/CRp/CRi as determined by investigator assessment per modified NCCN response criteria, MRD persistence prior to HSCT, or death due to any cause, whichever occurs first. HSCT (and CAR T-cell therapy) rate, defined as the number and percentage of participants being transplanted and those receiving CAR T-cell therapy after treatment with InO or ALLR3. OS, defined as the time from the date of randomization to the date of death due to any cause. Estimands: Not Applicable Safety: To evaluate the safety and tolerability of InO monotherapy vs ALLR3 induction Enpoints: Incidence and severity of AEs graded per NCI CTCAE v4.03. Estimands: Not Applicable Pharmacokinetics To evaluate the PK of InO npoints:Cmax and Ctrough Estimands: Not Applicable

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)