A Study of Inotuzumab Ozogamicin in Chinese Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
- Conditions
- Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT05687032
- Lead Sponsor
- Pfizer
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 44
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description inotuzumab ozogamicin 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
- Primary Outcome Measures
Name Time Method Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) per Investigator Assessment 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 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.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to approximately 2 years from first dose 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.
Overall Survival (OS) Up to approximately 2 years from first dose 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.
Percentage of Participants With Treatment-emergent Adverse Events Up to approximately 2 years from first dose 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)
Percentage of Participants With Laboratory Abnormalities Up to approximately 2 years from first dose Type and severity (including severity per National Cancer Institutes \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\], version 5.0)
Maximum Observed Inotuzumab Ozogamicin Serum Concentration (Cmax) Following Single and Multiple Dosing Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4 Cmax was the maximum observed concentration occurring between 0-8 hours post-dose.
Percentage of Participants With Anti-drug Antibodies (ADA) Day 1 of Cycle 1-6 and up to approximately 4 weeks (end of treatment [EoT]) from the last dose Analysis will be performed by central laboratory.
Pre-Dose Inotuzumab Ozogamicin Serum Concentration (Ctrough) Following Single and Multiple Dosing Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4 Ctrough was the concentration prior to subsequent dose (pre-dose) occurring after 8 hours.
Percentage of Participants With Neutralizing Antibodies (Nab). Day 1 of Cycle 1-6 and up to approximately 4 weeks (end of treatment [EoT]) from the last dose Analysis will be performed by central laboratory.
Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT) Up to approximately 2 years from first dose HSCT rate is defined as the percentage of participants who proceed to HSCT among participants who take at least one dose of inotuzumab ozogamicin.
Duration of Remission (DoR) for Participants Who Achieved CR/CRi Up to approximately 2 years from first dose 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。
Percentage of Participants Achieving MRD Negativity (Based on Central Laboratory Analysis) in Participants Achieving a CR/CRi Up to approximately 4 weeks (EoT) from last dose of study drug 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.
Trial Locations
- Locations (15)
Peking University Third Hospital
🇨🇳Beijing, Beijing, 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 Hospital of Harbin
🇨🇳Harbin, Heilongjiang, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Union Hospital, Tongji Medical College of Huazhong University of Science & Technology
🇨🇳Wuhan, Hubei, China
Tongji Hospital, Tongji Medical College,Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
West China Hospital of Sichuan University
🇨🇳Chengdu, Sichuan, China
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
🇨🇳Tianjin, China
The first Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical College
🇨🇳Wenzhou, Zhejiang, China