A Study of Inotuzumab Ozogamicin in Chinese Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This is an open-label, single-arm, multicenter study in Chinese patients with relapsed or refractory CD22-positive B-cell ALL. The objective of the study is to confirm the efficacy, safety, and PK of inotuzumab ozogamicin in patients with relapsed or refractory B-cell ALL from mainland China.

Official Title
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A PHASE 4, OPEN-LABEL, SINGLE-ARM, MULTICENTER STUDY OF INOTUZUMAB OZOGAMICIN IN CHINESE ADULT PATIENTS WITH RELAPSED OR REFRACTORY CD22-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: inotuzumab ozogamicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants, age 18 years or older at screening. Relapsed or refractory CD22-positive ALL. Subjects with Philadelphia chromosome-positive (Ph+) ALL must have failed standard treatment with at least one tyrosine kinase inhibitor. Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy. Patients with lymphoblastic lymphoma and bone marrow involvement ≥5% lymphoblasts by morphologic assessment. ECOG performance status 0-2. Adequate renal and hepatic function, and negative pregnancy test for women of childbearing potential. Exclusion Criteria: Subjects with isolated extramedullary relapse or active central nervous system (CNS) leukemia. Prior allogeneic hematopoietic stem cell transplant (HSCT) or other anti-CD22 immunotherapy within 4 months, or active graft versus host disease (GvHD) at study entry. Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: inotuzumab ozogamicin<br>Dose: inotuzumab ozogamicin 0.8-0.5 mg/m^2 IV, weekly, 3 times per cycle Cycle length: 21-28 days Total number of cycles: 6 | Drug: inotuzumab ozogamicin<br>* Given IV<br>* Other names: Besponsa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) per Investigator Assessment | CR was the disappearance of leukemia indicated by less than (<) 5 percent (%) marrow blasts & absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) greater than or equal to (≥)1000 per microliter (/μL) & platelets ≥100,000/μL. C1 extramedullary disease status (i.e. complete disappearance of measurable & non-measurable extramedullary disease with the following exceptions: for participants with at least 1 measurable lesion, all nodal masses greater than (>) 1.5 centimeters (cm) in greatest transverse diameter (GTD) at baseline must have regressed to less than or equal to (≤) 1.5 cm in GTD; all nodal masses ≥1 cm & ≤1.5 cm in GTD at baseline must have regressed to <1 cm GTD or reduced by 75% in sum of products of greatest diameters, no new lesions, spleen & other previously enlarged organs must have regressed in size & must not be palpable) was required. CRi was defined as CR except ANC <1000/μL &/or platelets <100,000/μL. | Screening, Day 16 to 28 of Cycles 1, 2 and 3, then every 1 to 2 cycles (or as clinically indicated) up to approximately 4 weeks (end of treatment [EoT]) from the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Remission (DoR) for Participants Who Achieved CR/CRi | DoR was defined as time from date of first response in responders (CR/CRi per Investigator assessment) to date of PFS event (i.e., death, progressive disease [objective progression, relapse from CR/CRi or treatment discontinuation due to global deterioration of health status] or starting new induction therapy or post-therapy stem cell transplant [SCT] without achieving CR/CRi). Participants without a DoR event at a time of analysis will be censored at the date of last valid disease assessment including follow-up disease assessment。 | Up to approximately 2 years from first dose | 
| Percentage of Participants Achieving MRD Negativity (Based on Central Laboratory Analysis) in Participants Achieving a CR/CRi | Bone marrow aspirate, collected at screening and for remission status and assessment of MRD. MRD will be assessed using NGS for rearranged IgH, IgK, and IgL receptor gene sequences at a central laboratory. MRD analysis will be done at least once in patients with prior assessment of CR or CRi. MRD-negativity will be defined as malignant B lymphocytes occurring at a frequency of <10^-4. | Up to approximately 4 weeks (EoT) from last dose of study drug | 
| Progression-Free Survival (PFS) | PFS was defined as time from date of randomization to earliest date of the following events: death, progressive disease (objective progression, relapse from CR/CRi or treatment discontinuation due to global deterioration of health status) and starting new induction therapy or post-therapy SCT without achieving CR/CRi. Participants without a PFS event at time of analysis were censored at the last valid disease assessment. In addition, participants with documentation of an event after an unacceptably long interval (>28 weeks if there was post-baseline disease assessment, or >12 weeks if there was no post-baseline assessment) since the previous disease assessment were censored at the time of the previous assessment (date of randomization if no post-baseline assessment). Post-study treatment follow-up disease assessments was included. Kaplan-Meier method used and 2-sided 95% confidence interval (CI) calculated based on the Brookmeyer and Crowley method. | Up to approximately 2 years from first dose | 
| Overall Survival (OS) | OS was defined as the time from first dose to date of death due to any cause. Participants last known to be alive were censored at date of last contact. | Up to approximately 2 years from first dose | 
| Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT) | HSCT rate is defined as the percentage of participants who proceed to HSCT among participants who take at least one dose of inotuzumab ozogamicin. | Up to approximately 2 years from first dose | 
| Percentage of Participants With Treatment-emergent Adverse Events | Type and severity (including severity per National Cancer Institutes [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0), including Veno-Occlusive Liver Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) (total, during study treatment, and post-HSCT) | Up to approximately 2 years from first dose | 
| Percentage of Participants With Laboratory Abnormalities | Type and severity (including severity per National Cancer Institutes [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0) | Up to approximately 2 years from first dose | 
| Maximum Observed Inotuzumab Ozogamicin Serum Concentration (Cmax) Following Single and Multiple Dosing | Cmax was the maximum observed concentration occurring between 0-8 hours post-dose. | Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4 | 
| Percentage of Participants With Anti-drug Antibodies (ADA) | Analysis will be performed by central laboratory. | Day 1 of Cycle 1-6 and up to approximately 4 weeks (end of treatment [EoT]) from the last dose | 
| Pre-Dose Inotuzumab Ozogamicin Serum Concentration (Ctrough) Following Single and Multiple Dosing | Ctrough was the concentration prior to subsequent dose (pre-dose) occurring after 8 hours. | Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4 | 
| Percentage of Participants With Neutralizing Antibodies (Nab). | Analysis will be performed by central laboratory. | Day 1 of Cycle 1-6 and up to approximately 4 weeks (end of treatment [EoT]) from the last dose |