InO - A Retrospective Study of UK Patients With Leukaemia (InO)

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

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.

Study Overview

• Status: Completed
• Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Intervention / Treatment: Drug: Inotuzumab Ozogamicin

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom, BS1 3NU
    • University Hospitals Bristol NHS Foundation Trust
  • London, United Kingdom, NW1 2PG
    • University College London Hospital NHS Foundation Trust
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust of Fulham Road
  • Taunton, United Kingdom, TA1 5DA
    • Taunton and Somerset NHS Foundation Trust of Musgrove Park Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with relapsed/refractory Acute Lymphoblastic Leukemia who are aged 18 and over and initiated Inotuzumab Ozogamicin between 1st of June 2016 and date of data collection and received treatment via NHS commissioning, via the Compassionate Use Programme, or via private purchase.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult R/R ALL patients who have received InO; 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; 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.; Other Names: CMC-544

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 6, 2020
• Primary Completion (ACTUAL): January 27, 2021
• Study Completion (ACTUAL): January 27, 2021

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (ACTUAL): July 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 21, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Inotuzumab Ozogamicin
• Other Study ID Numbers: X9001222

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No