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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: inotuzumab ozogamicin

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100091
      • Peking University Third Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510700
      • Sun Yat-sen University Cancer Center
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150010
      • The First Hospital of Harbin
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital, Tongji Medical College of Huazhong University of Science & Technology
    • Wuhan, Hubei, China, 430030
      • Wuhan Tongji Hospital
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College,Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital Of WenZhou Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: inotuzumab ozogamicin; 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; Given IV; Other Names: Besponsa

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2023
• Primary Completion (Estimated): August 7, 2024
• Study Completion (Estimated): November 7, 2025

Study Registration Dates

• First Submitted: January 6, 2023
• First Submitted That Met QC Criteria: January 6, 2023
• First Posted (Actual): January 17, 2023

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Immunoconjugates; Immunotoxins; Inotuzumab Ozogamicin
• Other Study ID Numbers: B1931034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes