A Study of Inotuzumab Ozogamicin in Chinese Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female participants, age 18 years or older at screening.
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Relapsed or refractory CD22-positive ALL.
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Subjects with Philadelphia chromosome-positive (Ph+) ALL must have failed standard treatment with at least one tyrosine kinase inhibitor.
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Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy.
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Patients with lymphoblastic lymphoma and bone marrow involvement ≥5% lymphoblasts by morphologic assessment.
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ECOG performance status 0-2.
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Adequate renal and hepatic function, and negative pregnancy test for women of childbearing potential.
Exclusion Criteria:
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Subjects with isolated extramedullary relapse or active central nervous system (CNS) leukemia.
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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.
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Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- B1931034