A Study of Patients Who Received Inotuzumab Ozogamicin for B-cell ALL (Acute Lymphoblastic Leukemia) That Occurred Again After the Last Treatment

A Retrospective Analysis of Inotuzumab Ozogamicin (InO) Usage in Adult Patients With Relapsed/Refractory (R/R) B-cell Acute Lymphoblastic Leukemia (ALL)

The purpose of the study was to understand the effectiveness and safety of the study medicine called Inotuzumab ozogamicin (InO) in patients with B-cell ALL in whom the disease occurred again after the last treatment.

This retrospective Study enroll adult patients who:

• were CD22 positive (a molecule in the body that stops the over activity of the immune system)
• Received only InO for the treatment of B-cell ALL that occurred again after the last treatment
• were Philadelphia chromosome positive (which occurs because of changes in genes)
• failed treatment with at least one Tyrosine Kinase Inhibitor (type of medicine that blocks the action of enzymes called tyrosine kinases which takes care of many cell functions, such as cell growth and division).

The patient data except their personal details are collected from a hospital based electronic medical record in India.

In this study the effectiveness and safety of InO will be studied after it was released to the market.

To do that, the study aims to gather details of B-cell ALL patients from 7 -10 hospitals across India:

• in whom the disease occurred again
• or those who never showed any improvement to earlier treatments
• now being treated with InO alone

Around 55 patients who have taken InO are likely to be enrolled in the study.

Then by using a statistical model and with all the information gathered, the safety and effectiveness of InO will be decided.

Study Overview

• Status: Completed
• Conditions: Adult Relapsed/Refractory B Cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Inotuzumab Ozogamicin

• Study Type: Observational
• Enrollment (Actual): 32

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110085
      • Rajiv Gandhi Cancer Institute And Research Centre
  • Haryana
    • Gurugram, Haryana, India, 122002
      • Fortis Memorial Research Institute
  • Kerala
    • Thalassery, Kerala, India, 670103
      • Malabar Cancer Center
  • Telangana
    • Hyderabad, Telangana, India, 500034
      • Indo-American Cancer & Research Centre
  • WEST Bengal
    • Kolkata, WEST Bengal, India, 700160
      • Tata Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia Patients

Description

Inclusion Criteria:

• Patients aged ≥18 years old at the initiation of InO treatment

  • Patients with relapsed/refractory B-cell ALL
  • Patients who initiated InO monotherapy between Feb'2017 and Feb'2022 and are CD22 positive
  • Ph+ patients who have failed treatment with at least 1 TKI

Exclusion Criteria:

• Patient not completing at least 1 cycle of InO therapy • Patient on InO in combination with chemotherapy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult relapsed or refractory B Cell ALL; Adult patients whose B Cell ALL has occurred again after the last treatment or patients who never responded to prior treatment	Drug: Inotuzumab Ozogamicin; Inotuzumab Ozogamicin is an Antibody drug conjugate directed against CD 22 positive B Cell ALL; Other Names: Besponsa; Inonza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved Complete Remission (CR) or Complete Remission With Incomplete Hematological Recovery (CRi) Following Treatment With InO	CR was defined as 5 percent (%) bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of [more than] >100*10^9 cells/liter [L] and absolute neutrophil count of >1*10^9 cells/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants Who Achieved Complete Remission (CR) or Complete Remission With Incomplete Hematological Recovery (CRi) Following Treatment With InO, Classified Per Number of Lines of Salvage Therapies Prior to InO Initiation	CR was defined as 5 percent (%) bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of [more than] >100*10^9 cells/liter [L] and absolute neutrophil count of >1*10^9 cells/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count. Salvage therapy is use of drugs after standard conventional chemotherapeutic regimens have failed to achieve remission.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants Who Achieved CR or CRi Following Treatment With InO, Classified Per High Burden and Low Burden Disease	CR was defined as 5% bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of >100*10^9 cells/L and absolute neutrophil count of >1*10^9 cells/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count. Disease burden was defined using percentage of bone marrow blasts (BMB). In this outcome measure low disease burden indicated BMB <50% and high disease burden indicated BMB >=50%.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved Minimal Residual Disease (MRD) Negativity Following Initiation of Ino 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. MRD was assessed by multicolor flow cytometry. CR was defined as 5% bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of >100*10^9/L and absolute neutrophil count of >1*10^9/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants Who Achieved MRD Negativity Classified Per Number of Lines of Salvage Therapies Following Initiation of InO 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. MRD was assessed by multicolour flow cytometry. CR was defined as 5% bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of >100*10^9/L and absolute neutrophil count of >1*10^9/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count. Salvage therapy is use of drugs after standard conventional chemotherapeutic regimens have failed to achieve remission. Participants with either CR or CRi who achieved MRD negativity classified per number of lines of salvage therapies are reported in this outcome measure.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants Who Achieved MRD Negativity Classified Per High Burden and Low Burden Disease Following Initiation of InO 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. MRD was assessed by multicolour flow cytometry. CR was defined as 5% bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of >100*10^9/L and absolute neutrophil count of >1*10^9/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count. Disease burden was defined using percentage of BMB. In this outcome measure low disease burden indicated BMB <50% and high disease burden indicated BMB >=50%. Participants with either CR or CRi who achieved MRD negativity classified per high burden and low burden disease are reported in this outcome measure.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants Achieving MRD Negativity Following Initiation of InO Among Those Who Had CR/CRi in Elderly Participants (>65 Years)	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. MRD was assessed by multicolour flow cytometry. CR was defined as 5% bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of >100*10^9/L and absolute neutrophil count of >1*10^9/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Median Number of Cycles of InO Treatment	The median number of cycles of InO a participant received during treatment were included. Standard dose of InO: 1.8 mg/m^2 per 21 days cycle.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Median Number of Cycles of InO Needed to Attain CR/CRi	CR was defined as 5% bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of >100*10^9/L and absolute neutrophil count of >1*10^9/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Mean Number of Cycles of InO Needed to Attain CR or CRi Classified Per Number of Lines of Salvage Therapies	CR was defined as 5% bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of >100*10^9/L and absolute neutrophil count of >1*10^9/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count. Salvage therapy is use of drugs after standard conventional chemotherapeutic regimens have failed to achieve remission.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Duration of Remission (DOR)	Remission was defined as either the reduction or disappearance of the signs and symptoms of leukemia for this study.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants Categorized as Per InO Doses	Standard dose of InO was 1.8 milligrams (mg) per meter square (m^2) per cycle. Under dose of InO was less than 1.8 mg/m^2 per cycle. Overdose of InO was more than 1.8 mg/m^2 per cycle.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants With InO Dose Modifications	Number of participants for whom there was deviation in InO dose from the standard dose (1.8 mg/ m^2 per cycle) were included.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants Who Received Concomitant Medications	Concomitant medication was defined as any medication other than, and in addition to, the study medication taken for any period of time during the treatment.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT)	HSCT is the transplantation of multipotent hematopoietic stem cells to treat some type of cancers and other diseases.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Survival Rate at 6 and 12 Months in Transplanted and Non-Transplanted Participants Who Achieved CR/CRi and MRD Negativity	Survival rate: percentage of participants in a study or treatment group who were still alive for a certain period of time after they were diagnosed with or started treatment for a disease. 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. MRD was assessed by multicolour flow cytometry. CR was defined as 5% bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of >100*10^9 cells/L and absolute neutrophil count of >1*10^9 cells/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count. In this outcome measure percentage of participants who had either CR or CRi with MRD negativity and survived at the end of 6 months and 12 months post initiation of InO treatment are reported on the basis of transplantation status.	6 and 12 months post initiation of InO treatment; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Survival Rate at 6 and 12 Months in Transplanted and Non-Transplanted Participants Classified Per Number of Lines of Salvage Therapies	Survival rate was defined as the percentage of participants in a study or treatment group who were still alive for a certain period of time after they were diagnosed with or started treatment for a disease. Salvage therapy is use of drugs after standard conventional chemotherapeutic regimens have failed to achieve remission. In this outcome measure percentage of transplanted and non-transplanted participants who survived at the end of 6 months and 12 months post initiation of InO treatment are classified based on number of lines of salvage therapies.	6 and 12 months post initiation of InO treatment; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Survival Rate at 6 and 12 Months in Transplanted and Non-Transplanted Participants Classified Per High Burden and Low Burden Disease	Survival rate was defined as the percentage of participants in a study or treatment group who were still alive for a certain period of time after they were diagnosed with or started treatment for a disease. Disease burden was defined using percentage of BMB. In this outcome measure low disease burden indicated BMB <50% and high disease burden indicated BMB >=50%. In this outcome measure percentage of transplanted and non-transplanted participants who survived at the end of 6 months and 12 months post initiation of InO treatment are classified based on high burden and low burden disease.	6 and 12 months post initiation of InO treatment; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Survival Rate at 6 and 12 Months in Transplanted and Non-Transplanted Elderly Participants (>65 Years)	Survival rate was defined as the percentage of participants in a study or treatment group who were still alive for a certain period of time after they were diagnosed with or started treatment for a disease. In this outcome measure percentage of transplanted and non-transplanted participants greater than 65 years of age, who survived at the end of 6 months and 12 months post initiation of InO treatment are reported.	6 and 12 months post initiation of InO treatment; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants Categorized According to Cause of Death		From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Relapse Free Survival (RFS) in All Participants and Participants With or Without Follow-up HSCT	RFS was defined as time from index date to the 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), or the start of new induction therapy or posttherapy HSCT without achieving CR/CRi. Index date was defined as the date of initiation of the first cycle of InO. CR was defined as 5% bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of >100*10^9/L and absolute neutrophil count of >1*10^9/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count. Median duration of relapse free survival in all participants included those participants who had achieved CR/CRi is reported in this outcome measure.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Percentage of HSCT Transplanted Participants With VOD and Percentage of HSCT Non-transplanted Participants With VOD	VOD occurs when the small blood vessels in the liver are blocked.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Percentage of Participants With VOD in Participants Classified Per Number of Lines of Salvage Therapies	VOD occurs when the small blood vessels in the liver are blocked. Salvage therapy is use of drugs after standard conventional chemotherapeutic regimens have failed to achieve remission.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Percentage of Participants With VOD Classified Per High Burden and Low Burden Disease	VOD occurs when the small blood vessels in the liver are blocked. Disease burden was defined using percentage of BMB. In this outcome measure low disease burden indicated BMB <50% and high disease burden indicated BMB >=50%.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Percentage of Participants With VOD in Elderly Participants (>65 Years)	VOD occurs when the small blood vessels in the liver are blocked.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants With Grade 3/4 Treatment Related Liver Toxicity (Hepatobiliary Disorder) Adverse Events (TEAEs) Following InO Initiation	Treatment-related AE was any untoward medical occurrence in a participant who has received the study drug. Liver toxicity parameters included: Aspartate aminotransferase (level) >=2.5*upper limit of normal (ULN); alanine transaminase (level) >=2.5*ULN and total serum bilirubin >=1.5*ULN. Here, Grade 3 indicates severe events and Grade 4 indicates Life-threatening events where urgent intervention was required.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants With Hematological Toxicities Following InO Initiation	Hematological toxicities included: Febrile neutropenia= absolute neutrophil count (ANC) < 1.0*10^9 cells/L, fever >=38.5 degree C); Neutropenia= absolute granulocyte count < 1.0*10^9 cells/L; Thrombocytopenia= platelet count < 150,000 platelets per microliter.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)
Number of Participants With Extramedullary Disease (EMD) or Lymphoblastic Lymphoma (LBL) Who Achieved CR or CRi	Extramedullary disease was the presence of leukemic cell aggregates in the form of solid tumor outside that of bone marrow. Lymphoblastic lymphoma, was a clonal hematopoietic stem cell disorder of B or T cell origin. CR was defined as 5% bone marrow blasts, no evidence of disease in the bone marrow, and recovery of peripheral blood count (platelet count of >100*10^9/L and absolute neutrophil count of >1*10^9/L). CRi was defined as 5% bone marrow blasts and no evidence of disease in the bone marrow, but with incomplete recovery of peripheral blood count.	From InO treatment initiation (Apr 2018) till end of follow-up (Apr 2023) [Maximum up to 61 Months]; data retrospectively collected from 08-Mar-2023 to 10-Jul-2023 (approximately 4 months of this study)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, 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): March 8, 2023
• Primary Completion (Actual): July 10, 2023
• Study Completion (Actual): July 10, 2023

Study Registration Dates

• First Submitted: October 24, 2022
• First Submitted That Met QC Criteria: October 24, 2022
• First Posted (Actual): October 27, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Relapsed ALL; Refractory Acute Lymphoblastic Leukemia; Refractory ALL; Adult Relapsed/Refractory ALL; Adult ALL; Relapsed B Cell ALL; Refractory B Cell ALL; Relapsed Acute Lymphoblastic Leukemia
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; Immunotoxins; Inotuzumab Ozogamicin
• Other Study ID Numbers: B1931043; NCT05597085 (Registry Identifier: ClinicalTrials.gov)

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes