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

• ClinicalTrials.gov Identifier: NCT05748171
• Recruitment Status: Recruiting
• First Posted: February 28, 2023
• Last Update Posted: April 30, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: January 20, 2023
• First Posted Date: February 28, 2023
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: May 17, 2023
• Estimated Primary Completion Date: July 11, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2023)

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) [ Time Frame: After 1 treatment cycle: Day 28 +/- 2 days ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 17, 2023)

• Event Free Survival (EFS) [ Time Frame: From study start to first event (progression, relapse, failure to achieve CR/CRp/CRi by the end of induction, MRD persistence prior to HSCT [hematopoietic stem cell transplant], second malignancy, or death): up to 5 years from randomization ]
  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 [ Time Frame: From date of first response to date of first event (objective progression, relapse as determined by investigator assessment, MRD persistence prior to HSCT, or death due to any cause, whichever occurs first): up to 5 years from End of Treatment ]
  DoR will be summarized using Kaplan-Meier methods.
• Rate of hematopoietic stem cell transplantation (HSCT) [ Time Frame: Up to 5 years from randomization ]
  HSCT rate will be summarized by descriptive analyses (ie, percentage of participants who underwent HSCT after treatment).
• Overall Survival (OS) [ Time Frame: From start of treatment to date of death due to any cause: up to 5 years from randomization ]
  OS will be summarized by treatment arm using Kaplan-Meier methods.
• Number of participants reporting an Adverse Event (AE) [ Time Frame: From time of informed consent up to a minimum of 60 calendar days after the last dose of study drug. ]
  The number and percentage of participants who experienced any AE, SAE (Serious Adverse Event), treatment related AE, and treatment related SAE will be summarized according to worst toxicity grades.
• Pharmacokinetics (PK) parameter: InO Cmax [ Time Frame: 1 treatment cycle: 28 days ]
  Descriptive summary statistics will be provided for InO serum concentrations at scheduled visits.
• Number of Adverse Events (AE) reported by severity [ Time Frame: From time of informed consent up to a minimum of 60 calendar days after the last dose of study drug. ]
  AEs will be graded by the investigator according to the CTCAE (Common Terminology Criteria for Adverse Events) version 4.03.
• Pharmacokinetics (PK) parameter: InO trough levels [ Time Frame: 1 treatment cycle: 28 days ]
  Descriptive summary statistics will be provided for InO serum concentrations at scheduled visits.
• Rate of Chimeric antigen receptor (CAR) T-cell therapy [ Time Frame: Up to 5 years from randomisation ]
  CAR T-cell therapy rate will be summarized by descriptive analyses (ie, the number, percent of participants who underwent CAR T-cell therapy after treatment).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

• Study Type: Interventional
• Study Phase: Phase 2

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

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: ACUTE LYMPHOBLASTIC LEUKEMIA

Intervention

• Drug: Inotuzumab ozogamicin
  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.
  Other Name: Besponsa
• Drug: ALLR3
  The ALLR3 chemotherapy regimen (vincristine, mitoxantrone, dexamethasone, and asparaginase) has been adopted by pediatric oncology groups as treatment for pediatric relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL)
  Other Name: R3

Study Arms

• Experimental: Inotuzumab ozogamicin

  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
  Intervention: Drug: Inotuzumab ozogamicin
• Active Comparator: ALLR3

  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

  Intervention: Drug: ALLR3

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 17, 2023): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 9, 2031
• Estimated Primary Completion Date: July 11, 2028 (Final data collection date for primary outcome measure)

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 (ie, KMT2A-rearrangements, TCF3-HLF, TCF3-PBX1, hypodiploidy, 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.

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: Austria, Belgium, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, Norway, Poland, Slovakia, Spain, Sweden, Switzerland

Administrative Information

• NCT Number: NCT05748171
• Other Study ID Numbers: B1931036; EU PIP Study #2 ( Other Identifier: Alias Study Number ); 2022-000186-40 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2024