InO - A Retrospective Study of UK Patients With Leukaemia

Study Overview
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Brief Summary
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The purpose of this study is to describe the demographics and clinical characteristics, treatment pathway, and effectiveness and safety of inotuzumab ozogamicin in patients with relapsed/refractory B-cell acute lymphoblastic leukaemia treated with inotuzumab ozogamicin in the real-world.

Official Title
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A Retrospective Chart Review of UK Patients With Relapsed/Refractory Acute Lymphoblastic Leukaemia Treated With Inotuzumab Ozogamicin, a Real World Research Study

Conditions
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Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention / Treatment
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* Drug: Inotuzumab Ozogamicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with relapsed/refractory ALL. Patients who initiated InO between 1st of June 2016 and date of data collection. Patients who accessed InO treatment via NHS commissioning, via the CUP, or via private purchase. Patient aged ≥18 years old at initiation of InO treatment Exclusion Criteria: Patients initiated on treatment with InO at a different hospital than the ones selected in this study. Patients with <3 months of follow-up since index date, unless death occurs <3 months from index date.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adult R/R ALL patients who have received InO<br>Relapsed/refractory ALL patients who are 18 years and over and initiated InO between 1st of June 2016 and date of data collection (to be confirmed). They will have accessed InO treatment via NHS commissioning, via the CUP, or via private purchase and will have at least 3 months follow up from the index date unless death occurs within that time. | Drug: Inotuzumab Ozogamicin<br>* Inotuzumab ozogamicin is an antibody-drug conjugate (ADC) composed of a recombinant humanised IgG4 kappa CD22-directed monoclonal antibody (produced in Chinese hamster ovary cells by recombinant DNA technology) that is covalently linked to N-acetyl-gamma-calicheamicin dimethylhydrazide.<br>* Other names: CMC-544;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Received First Line Chemotherapy According to National Trial or Treatment Guideline | In this outcome measure, number of participants who were treated with the first-line chemotherapy during anytime between initial diagnosis of ALL and InO initiation, were reported. | Anytime between initial diagnosis of ALL and InO initiation, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants According to Number of Lines of Salvage Therapy | In this outcome measure, number of participants according to number of lines of salvage therapy anytime between initial diagnosis of ALL and InO initiation, were reported. | Anytime between initial diagnosis of ALL and InO initiation, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants According to Prior Hematopoietic Stem Cell Transplant (HSCT) | In this outcome measure, number of participants, who were treated with hematopoietic stem cell transplant (HSCT) before initiation of InO, were reported. | Anytime between initial diagnosis of ALL and InO initiation, during data identification period from June 2016 to January 2021 (approximately 4.5 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants According to Type of Conditioning Regimen for Each HSCT | In this outcome measure, number of participants were classified according to different type of conditioning regimen for each HSCT (high-dose intensity myeloablative, reduced-intensity/non-myeloablative), were reported. | Anytime between initial diagnosis of ALL and InO initiation, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Who Were Treated Previously With Blinatumomab | In this outcome measure, number of participants who were previously treated with blinatumomab, were reported. | Anytime between initial diagnosis of ALL and InO initiation, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Treated With Chimeric Antigen Receptor (CAR) T-Cell Therapies | In this outcome measure, number of participants treated with chimeric antigen receptor (CAR) T-cell therapies before initiation of InO, were reported. | Anytime between initial diagnosis of ALL and InO initiation, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Duration of Treatment With Inotuzumab Ozogamicin | In this outcome measure, total duration of InO treatment was reported. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants According to Number of Inotuzumab Ozogamicin Treatment Cycles | In this outcome measure, number of participants were classified according to total number of InO treatment cycles received. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants According to Interrupted Inotuzumab Ozogamicin Treatment Cycles | In this outcome measure, number of participants were classified according to number of interrupted cycles of InO treatment. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants According to Reasons for Inotuzumab Ozogamicin Treatment Interruption | In this outcome measure, number of participants, were reported according to reasons of interruption in respective Cycles. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants According to Prescribed Inotuzumab Ozogamicin Doses | In this outcome measure, number of participants according to prescribed starting InO dose, were reported. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Classified on the Basis of Any Modifications in Inotuzumab Ozogamicin Dose | In this outcome measure, number of participants were classified as following: 1) with no dose modification and 2) no data recorded. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Who Were Treated With Concomitant Azole Antifungal Therapy | In this outcome measure, number of participants who were treated with concomitant azole antifungal therapy along with InO treatment were reported. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Duration of Concomitant Azole Antifungal Therapy | In this outcome measure, time/duration between start date and end date of concomitant azole antifungal, was reported. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Who Achieved Complete Remission (CR) by the End of InO Treatment | CR was defined as documented in medical records or (if unavailable in the records) as less than (<) 5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets greater than or equal to [>=] 100*10^9 cells per liter [/L] and absolute neutrophil counts [ANC] >=1*10^9 cells/L) and resolution of any extramedullary disease. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Who Achieved CR With Incomplete Hematological Recovery (CRi) by the End of InO Treatment | CRi was defined as documented in medical records or (if unavailable in the records) <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets <100* 10^9 cells/L and ANC <1*10^9 cells/L) and resolution of any extramedullary disease. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants With CR/CRi by the End of InO Treatment | In this outcome, number of participants who achieved CR/CRi at the end of InO treatment are reported. CR was defined as documented in medical records or as <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets >=100*10^9 cells/L and ANC >=1*10^9 cells/L) and resolution of any extramedullary disease. CRi was defined as documented in medical records or <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets <100*10^9 cells/L and ANC <1*10^9 cells/L) and resolution of any extramedullary disease. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Median Time to CR/CRi | CR was defined as documented in medical records or as <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets >=100*10^9 cells/L and ANC >=1*10^9 cells/L) and resolution of any extramedullary disease. CRi was defined as documented in medical records or <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets <100*10^9 cells/L and ANC <1*10^9 cells/L) and resolution of any extramedullary disease. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Who Achieved Negative Minimal Residual Disease (MRD) Among Those Who Had CR/CRi | Negative MRD was defined as documented in medical records or (if unavailable in the records) as leukemic cells comprising <1*10^-4 (<0.01%) of bone marrow nucleated cells. This outcome measure was analyzed in participants with CR/CRi. CR was defined as documented in medical records or as <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets >=100*10^9 cells/L and ANC >=1*10^9 cells/L) and resolution of any extramedullary disease. CRi was defined as documented in medical records or <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets <100*10^9 cells/L and ANC <1*10^9 cells/L) and resolution of any extramedullary disease. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Who Achieved Negative MRD Classified Per InO Cycles | Negative MRD (among those who had CR/CRi) was defined as documented in medical records or (if unavailable in the records) as leukemic cells comprising <1*10^-4 (<0.01%) of bone marrow nucleated cells. CR was defined as documented in medical records or as <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets >=100*10^9 cells/L and ANC >=1*10^9 cells/L) and resolution of any extramedullary disease. CRi was defined as documented in medical records or <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets <100*10^9 cells/L and ANC <1*10^9 cells/L) and resolution of any extramedullary disease. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Who Survived at 3, 6 and 12 Months Post InO Treatment Initiation | In this outcome measure, number of participants who survived 3, 6, and 12 post InO treatment, were reported. | At 3, 6, and 12 months post InO initiation date, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Classified According to Their Cause of Death | In this outcome measure, number of participants according to their cause of death were reported. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Overall Survival (OS) | OS was defined as the time from the index date to the date of death. Participants were censored at date of latest visit at the time of data collection. Kaplan-Meier method was used for OS analysis. | InO initiation date to death due to any cause or last visit at time of data collection, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Percentage of Participants Who Were Relapse-free at 3, 6 and 12 Months Post InO Treatment Initiation | Relapse free survival: the time from the start of treatment to earliest date of the following events: death, progressive disease (including objective progression, relapse from CR/CRi, treatment discontinuation due to global deterioration of health status), and start of new induction therapy or post-therapy HSCT without achieving CR/CRi; as documented in medical records. CR: documented in medical records or as <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets >=100*10^9/L and ANC >=1*10^9/L) and resolution of any extramedullary disease. CRi: documented in medical records or <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets <100*10^9/L and ANC <1*10^9/L) and resolution of any extramedullary disease. Progressive disease (PD): a doubling of peripheral blasts with an absolute increase of >5*10^9 cells/L. | At 3, 6, and 12 months from InO initiation date, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Relapse-free Survival (RFS) | RFS was defined as the time from the start of treatment to earliest date of the following events: death, PD (including objective progression, relapse from CR/CRi, treatment discontinuation due to global deterioration of health status), and start of new induction therapy or post-therapy HSCT without achieving CR/CRi; as documented in medical records. CR was defined as documented in medical records or as <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets >=100*10^9 cells /L and ANC >=1*10^9 cells/L) and resolution of any extramedullary disease. CRi was defined as documented in medical records or <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets <100*10^9 cells/L and ANC <1*10^9 cells/L) and resolution of any extramedullary disease. PD: a doubling of peripheral blasts with an absolute increase of >5*10^9 cells/L. | From InO initiation date to death or progressive disease, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Time to Non-relapse Mortality (NRM) | NRM was defined as the time from the date of follow-up HSCT until death due to any cause without disease progression or relapse. | Post InO treatment from date of follow up HSCT to death, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants According to Types of Therapies Post Inotuzumab Ozogamicin Treatment | In this outcome measure, number of participants according to therapies they initiated post InO treatment were reported. One participant could have more than 1 type of therapies. | Post InO treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Who Achieved CR, CRi, Progressive Disease and Stable Disease With Different Types of Post Inotuzumab Ozogamicin Treatments | CR was defined as documented in medical records or as <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets >=100*10^9 cells/L and ANC >=1*10^9 cells/L) and resolution of any extramedullary disease. CRi was defined as documented in medical records or <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets <100*10^9 cells/L and ANC <1*10^9 cells/L) and resolution of any extramedullary disease. PD was defined as a doubling of peripheral blasts with an absolute increase of >5*10^9 cells/L. Stable disease was defined as increase of peripheral blasts with an absolute increase not >50%. | Post InO treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Who Survived Post InO Blinatumomab Treatment | In this outcome measure, number of participants who survived at completion of InO treatment were reported. | Post InO treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Who Experienced a Documented Diagnosis of Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) Post InO Treatment | VOD, also called SOS, happens when the small blood vessels that lead into the liver and are inside the liver become blocked. | Post InO treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants According to Type of Treatments Received for Documented Diagnoses of Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) | VOD, also called SOS, happens when the small blood vessels that lead into the liver and are inside the liver become blocked. | Post InO treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants Who Survived Following Treatment For Documented Diagnoses of Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) | VOD, also called SOS, happens when the small blood vessels that lead into the liver and are inside the liver become blocked. | Post InO treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants With Interrupted InO Treatment Due to VOD/SOS | VOD, also called SOS, happens when the small blood vessels that lead into the liver and are inside the liver become blocked. | Post InO treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants With Moderate Severity VOD/SOS | VOD, also called SOS, happens when the small blood vessels that lead into the liver and are inside the liver become blocked. | Post InO Treatment, during data identification period from June 2016 to January 2021 (approximately 4.5 years); from the data collected and observed retrospectively over approximately 12 months of this study | 
| Number of Participants Who Experienced Grade 3 and Grade 4 (Lung/Cardiac/Kidney/Liver) Treatment Related Adverse Event (TRAE) Following Inotuzumab Ozogamicin Initiation | Adverse event (AE) was defined as any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 were severe events. Grade 4 were life-threatening events. Information for grades was recorded as per participants' medical records. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants According to Types of Treatments Received for Grade3/4 TRAE Following Inotuzumab Ozogamicin Initiation | AE was defined as any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 were severe events. Grade 4 were life-threatening events. Information for grades was recorded as per participants' medical records. | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants With Liver Dysfunction Following Inotuzumab Ozogamicin Initiation |  | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants With Peripheral Blood Blast Counts Measurement Prior to Post InO HSCT |  | Prior to post InO HSCT, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study | 
| Number of Participants With Significant Risk Factors for VOD/SOS | In this outcome measure, participants with significant risk factor for VOD/ SOS occurrence were reported. VOD, also called SOS, happens when the small blood vessels that lead into the liver and are inside the liver become blocked | From InO initiation date to date of end of treatment, during data identification period from June 2016 to January 2021 (approximately 4.7 years); retrieved data was analyzed during 12 months of this observational study |