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

Pfizer

Status and phase: Enrolling; Phase 2

Conditions: ACUTE LYMPHOBLASTIC LEUKEMIA

Treatments: Drug: ALLR3; Drug: Inotuzumab ozogamicin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05748171

B1931036

2022-000186-40 (EudraCT Number)

EU PIP Study #2 (Other Identifier)

2023-509810-13-00 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 1 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Inotuzumab ozogamicin

Experimental group

Description:

Each participant in the InO arm will receive 1 course (3 doses) of InO, as follows: * Day 1: 0.8 mg/m2 * Days 8 (±1 day) and Day 15 (±1 day): 0.5 mg/m2/dose

Treatment:

Drug: Inotuzumab ozogamicin

ALLR3

Active Comparator group

Description:

Mitoxantrone 10 mg/m2 on Days 1 and 2 Vincristine 1.5 mg/m2 (max single dose 2 mg) administered on Days 3, 10, 17 and 24 Dexamethasone 20 mg/m2/day administered orally (or IV) divided into two daily doses (maximum 40 mg/day) as two 5-day blocks on Days 1-5 and Days 15-19. PEG-asparaginase 1000 units/m2 IV administered on Days 3 and 17. In case of hypersensitivity/allergic reaction to PEG-asparaginase, each dose of PEG-asparaginase will be replaced by Erwinia-asparaginase at a dose of 20,000 units/m² IV or IM every other day for a total of 6 doses

Treatment:

Drug: ALLR3