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

Pfizer44 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Lymphoblastic Leukemia

Interventions

inotuzumab ozogamicinDRUG

Given IV

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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).

Locations (16)

Peking University Third Hospital

Beijing, Beijing Municipality, China

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Outcomes

Primary Outcomes

Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematological Recovery (CRi) as Per Investigator's Assessment According to a Modified Cheson Criteria

CR: disappearance of leukemia as indicated by \<5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) \>=1000 per microliter (/mcL) and platelets \>=100,000/mcL. C1 extramedullary disease (EMD) status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 centimeter (cm) in greatest transverse diameter (GTD) at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=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 (SPD). No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases were assessed using the same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<100,000/mcL.

Time frame: From InO treatment initiation on Day 1 to CR or CRi (maximum up to 30.1 weeks of treatment exposure)

Secondary Outcomes

Duration of Remission (DoR)

DoR: from date of first CR/CRi to date of disease progression (objective progression, relapse from CR/CRi), death due to any cause, whichever occurred first. CR: disappearance of leukemia as indicated by \<5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC \>=1000 per microliter (/mcL) and platelets \>=10\^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 cm in GTD at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<10\^5/mcL.

Data from ClinicalTrials.gov

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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

...and 6 more locations

Time frame: From date of first response in responders (CR/CRi) to the date of disease progression (objective progression, relapse from CR/CRi), death due to any cause, whichever occurred first (including post-study treatment follow-up disease assessment)

Percentage of Participants With Minimal Residual Disease (MRD) Negativity Among Who Achieved CR/CRi

MRD negativity was defined as malignant B lymphocytes occurring at frequency \<10\^4. CR: disappearance of leukemia as indicated by \<5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC \>=1000 per microliter (/mcL) and platelets \>=10\^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 cm in GTD at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<10\^5/mcL.

Time frame: From CR/CRi till MRD negativity achieved (maximum up to 30.1 weeks of treatment exposure)

Progression-free Survival (PFS)

PFS: from date of first dose to date of disease progression (objective progression, relapse from CR/CRi), or death due to any cause, whichever occurred first. CR: disappearance of leukemia as indicated by \<5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC \>=1000 per microliter (/mcL) and platelets \>=10\^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 cm in GTD at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<10\^5/mcL.

Time frame: From date of first dose to the date of disease progression (objective progression, relapse from CR/CRi), or death due to any cause, whichever occurred first

Overall Survival (OS)

OS was defined as the time from date of first dose to the date of death due to any cause. Participants without confirmation of death were to be censored on date of last contact.

Time frame: From date of first dose to the date of death due to any cause or censoring, whichever occurred first

Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT)

Participants who proceeded to HSCT was reported. HSCT is a procedure where multipotent hematopoietic stem cells are transplanted from sources such as bone marrow, peripheral blood, or umbilical cord blood. These stem cells can replicate inside a participant and produce additional normal blood cells.

Time frame: From InO treatment initiation till study completion

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated; Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if the event start date is during the on-treatment period (including on the date of first dose).

Time frame: From InO treatment initiation till study completion

Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) Based on NCI CTCAE Version 5

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if the event start date is during the on-treatment period (including on the date of first dose).

Time frame: From InO treatment initiation till study completion

Number of Participants With TEAEs - Treatment Related Based on NCI CTCAE Version 5

An AE was defined as any untoward medical occurrence in a participant temporally associated with use of study intervention, whether or not considered related to study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if event start date is during on-treatment period (including on date of first dose). Relatedness to study drug was assessed by investigator.

Time frame: From InO treatment initiation till study completion

Number of Participants With AEs According to Severity Based on NCI CTCAE Version 5

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE.

Time frame: From InO treatment initiation till study completion

Number of Participants With Hematology Laboratory Parameters of Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

Hematology parameters included white blood cell count (with differential including blast count1), hemoglobin and platelet count. Grade 2: moderate; minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care; Grade 4: life-threatening consequences.

Time frame: From InO treatment initiation till study completion

Number of Participants With Hematology Chemistry Parameters of Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

Chemistry parameters included sodium, potassium, magnesium, calcium, creatinine, albumin, alanine aminotransferase, aspartate aminotransferase, glucose, phosphorus, total bilirubin, direct bilirubin only if total is elevated, blood urea nitrogen or urea, uric acid or urate, alkaline phosphatase, lactate dehydrogenase, gamma glutamyl transpeptidase, total protein, amylase and/or lipase. Grade 2: moderate; minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care; Grade 4: life-threatening consequences.

Time frame: From InO treatment initiation till study completion

Number of Participants With Veno-occlusive Disease (VOD)

Criteria for VOD were defined as (i) classical VOD (first 21 days after HSCT): bilirubin greater than or equal to 2 mg/dL and two (or more) of the following criteria must also be present; painful hepatomegaly, weight gain \>5%, ascites. (ii) late onset VOD (\>21 days after HSCT): classical VOD beyond day 21 or histologically proven VOD; or two or more of the following criteria must be present: bilirubin \>2 mg/dL; painful hepatomegaly; weight gain \>5%; ascites.

Time frame: From InO treatment initiation till study completion

Maximum Plasma Concentration (Cmax) of InO on Day 1 of Cycle 1 and Cycle 4

Cmax was defined as maximum observed plasma concentration. Cmax was observed directly from data.

Time frame: Cycle 1: Pre-dose (0 hour), 1, 2 and 4 hours post-dose on Day 1; Cycle 4: Pre-dose (0 hour), and 1 hour post-dose on Day 1

Pre-dose Concentration (Ctrough) of InO on Day 1 of Cycle 4

Ctrough was observed directly from data.

Time frame: Pre-dose (0 hour) on Day 1 of Cycle 4

Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb) to InO

A participant was ADA or NAb positive if (i) baseline titer was missing or negative and participant had \>=1 post treatment positive titer (treatment-induced), or (ii) positive titer at baseline and had a \>=0.602 unit increase in titer (log10) from baseline in \>=1 post-treatment sample (treatment-boosted).

Time frame: From InO treatment initiation till study completion