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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05687032
• Other study ID #: B1931034
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: February 24, 2023
• Est. completion date: November 7, 2025

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 44
• Est. completion date: November 7, 2025
• Est. primary completion date: August 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• inotuzumab ozogamicin
Given IV

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	NanFang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The first Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Hospital of Harbin	Harbin	Heilongjiang
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang
China	Tongji Hospital, Tongji Medical College,Huazhong University of Science and Technology	Wuhan	Hubei
China	Union Hospital, Tongji Medical College of Huazhong University of Science & Technology	Wuhan	Hubei
China	Wuhan Tongji Hospital	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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