Inotuzumab Ozogamicin in the Treatment of MRD+ After HSCT of ALL

A Multicenter Prospective Clinical Study of Inotuzumab Ozogamicin (INO) in the Treatment of Minimal Residual Disease Recurrent After Hematopoietic Stem Cell Transplantation of Acute Lymphoblastic Leukemia (ALL)

As part of postremission consolidative therapy, the decision to proceed with hematopoietic stem cell transplantation is a recommendable regimen in ALL therapy. However, The recurrence rate is high after transplantation. Minimal Residual Disease (MRD) is an important factor affecting the effect of HSCT. The hematologic recurrence rate of MRD-positive patients with adult ALL is high.

MRD- is associated with better prognosis. Therefore, maintaining MRD- after transplantation is necessary for long-term survival. The purpose of this study is to explore the efficacy and safety of Inotuzumab Ozogamicin in the treatment of minimal residual disease recurrence after HSCT of ALL patients.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic Stem Cell Transplantation; ALL; MRD-positive
• Intervention / Treatment: Drug: Inotuzumab Ozogamicin

Detailed Description

As part of postremission consolidative therapy, the decision to proceed with hematopoietic stem cell transplantation is a recommendable regimen in ALL therapy. However, The recurrence rate is high after transplantation. Minimal Residual Disease (MRD) is an important factor affecting the effect of HSCT. The hematologic recurrence rate of MRD-positive patients with adult ALL is high.

MRD- is associated with better prognosis. Therefore, maintaining MRD- after transplantation is necessary for long-term survival. INO-VATE confirmed that Inotuzumab Ozogamicin can be used to achieve high remission (CR/CRi) and MRD-negative rates, serving as an effective bridge to HSCT, and it is associated with increased OS and PFS in patients with R/R BCP ALL. The purpose of this study is to explore the efficacy and safety of Inotuzumab Ozogamicin in the treatment of minimal residual disease recurrence after HSCT of ALL patients.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sheng-Li Xue, MD; Phone Number: 0086-0512-67781139; Email: slxue@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Sheng-Li Xue, M.D.; Phone Number: 0086-0512-67781139; Email: slxue@suda.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged ≥ 15 and ≤ 65 years.
2. Patients diagnosed with CD22+ B-ALL according to 2023 NCCN Acute Lymphoblasts Leukaemias diagnosis standard.
3. CD22+ B-ALL patients with MRD recurrence after HSCT. Ph+ ALL patients were eligible if treatment with 1 or more second-generation BCR::ABL1 tyrosine kinase inhibitors (TKIs) had failed,
4. ECOG performance status score less than 3.
5. Expected survival time #3 months.
6. Patients without serious heart, lung, liver, or kidney disease.
7. Ability to understand and voluntarily provide informed consent.

Exclusion Criteria:

1. Patients who are allergic to the study drug or drugs with similar chemical structures.
2. Pregnant or lactating women, and women of childbearing age who do not want to practice effective methods of contraception.
3. Active infection.
4. Active bleeding.
5. Patients with new thrombosis, embolism, cerebral hemorrhage, or other diseases or a medical history within one year before enrollment.
6. Patients with mental disorders or other conditions whereby informed consent cannot be obtained and where the requirements of the study treatment and procedures cannot be met.
7. Liver function abnormalities (total bilirubin > 1.5 times the upper limit of the normal range, ALT/AST > 2.5 times the upper limit of the normal range or patients with liver involvement whose ALT/AST > 1.5 times the upper limit of the normal range), or renal anomalies (serum creatinine > 1.5 times the upper limit of the normal value).
8. Patients with a history of clinically significant QTc interval prolongation (male > 450 ms; female > 470 ms), ventricular heart tachycardia and atrial fibrillation, II-degree heart block, myocardial infarction attack within one year before enrollment, and congestive heart failure, and patients with coronary heart disease who have clinical symptoms and requiring drug treatment.
9. Surgery on the main organs within the past six weeks.
10. Drug abuse or long-term alcohol abuse that would affect the evaluation results.
11. Patients who have received organ transplants (excepting bone marrow transplantation).
12. Patients not suitable for the study according to the investigator's assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inotuzumab Ozogamicin in the Treatment of MRD+ After HSCT of ALL; intravenous infusion: Cycle 1: D1 0.8mg/m2, D8 0.5mg/m2, D15 0.5mg/m2, if the MRD turn negative, cycle 2: D1 0.5mg/m2, D8 0.5mg/m2, D15 0.5mg/m2， if not，cycle 2: D1 0.8mg/m2, D8 0.5mg/m2, D15 0.5mg/m2	Drug: Inotuzumab Ozogamicin; intravenous infusion: Cycle 1: D1 0.8mg/m2, D8 0.5mg/m2, D15 0.5mg/m2, if the MRD turn negative, cycle 2: D1 0.5mg/m2, D8 0.5mg/m2, D15 0.5mg/m2， if not，cycle 2: D1 0.8mg/m2, D8 0.5mg/m2, D15 0.5mg/m2; Other Names: INO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rate of MRD-	For Ph-negative ALL: undetectable MRD by flow cytometry At the end of Cycle 1 and Cycle 2 (each cycle is 21 days) . For Ph-positive ALL: undetectable MRD by flow cytometry and absence of quantifiable BCR::ABL1 transcript by PCR At the end of Cycle 1 and Cycle 2(each cycle is 21 days).	At the end of Cycle 1 and Cycle 2(each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	It is measured from the date of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.	1 year
Adverse events in other organs or systems	Record of adverse events in other organs or systems during and after designed venetoclax combined azacitidine regimen induction.	1 year
Progression-Free Survival (PFS)	It is measured from the date of entry into this trial to the date of progression or death	1 year
Adverse events in hematological system	Record of adverse events in hematological system during and after designed venetoclax combined azacitidine regimen induction	1 year

Collaborators and Investigators

• Sponsor: Sheng-Li Xue, MD
• Collaborators: Northern Jiangsu Province People's Hospital; The Second People's Hospital of Huai'an; First Affiliated Hospital Bengbu Medical College; Jining Medical University; Affiliated Hospital of Nantong University; Suzhou Hospital of Traditional Chinese Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: July 1, 2023
• First Submitted That Met QC Criteria: July 8, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Immunoconjugates; Immunotoxins; Inotuzumab Ozogamicin
• Other Study ID Numbers: szINO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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