Blinatumomab Plus Venetoclax Sequenced With Inotuzumab Ozogamicin in Treating B-ALL

August 14, 2024 updated by: First Affiliated Hospital of Zhejiang University

The Regimen of Blinatumomab and Venetoclax Sequenced With Inotuzumab Ozogamicin in Treating Precursor B Cell Acute Lymphoblastic Leukemia: A Phase II, Single Arm and Multicenter Study

Precursor B cell acute lymphoblastic leukemia (B-ALL) is an aggressive type of leukemia, with high relapse rate and poor long term survival in adults. Traditional treatment regimens mainly include chemotherapy and hematopoietic stem cell transplantation. In the past decade, with the application of molecular targeted drugs and immunotherapy, the survival of B-ALL patients has significantly improved. In this study，we propose a treatment approach that combines Blinatumomab and Venetoclax sequenced with Inotuzumab Ozogamicin in B-ALL adults. Our study aims to answer the safety and efficacy of this treatment regimen, and further improve the survival for those participants.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, single-arm, phase II and open-label study. A total of 20 Ph-negative B-ALL participants will be enrolled. The primary endpoint is 2-year event free survival(EFS).

The induction therapy is a combination of Blinatumomab(Blina), Venetoclax(Ven) and Dexamethasone(DXM), and would be applied for two cycles. As for consolidation, the Inotuzumab Ozogamicin(INO) would be given on cycle 3 and cycle 5. The high dose of MTX would be given on Cycle 4 and the Ven plus L-asp would ben given on Cycle 6. Subsequent maintenance therapy contains of low dose of Chemotherapy, Blina and INO.

The purpose of this study is to explore the safety and efficacy of the whole-process management of multi-drug combination regimen in the treatment of newly diagnosed Ph-negative B-ALL patients.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • Recruiting
        • The First Affiliated Hospital, Zhejiang University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Before enrollment, a diagnosis of newly diagnosed precursor B-cell acute lymphoblastic leukemia with Philadelphia chromosome-negative must be confirmed. The diagnostic criteria refer to the 2022 WHO classification.
  2. Age ≥ 40 years;
  3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
  4. Expected survival time ≥ 3 months;
  5. No organ dysfunction that would restrict the use of this protocol during the screening period;
  6. Understand the study and sign the informed consent form.
  7. Men, women of childbearing age (only postmenopausal women who have been menopausal for at least 12 months can be considered infertile), and their partners voluntarily take effective contraceptive measures deemed effective by the investigator during the treatment period and for at least 12 months after the last dose of the study drug.

Exclusion Criteria:

  1. Patients with known central nervous system (CNS) involvement of ALL;
  2. Diseases with abnormal heart, lung, liver, kidney, or other organ functions that may limit the patient's participation in this trial (including but not limited to severe infections, uncontrolled diabetes, severe heart failure or angina, active pulmonary tuberculosis, asthma, COPD, bronchiectasis, etc.);
  3. Cardiac ultrasound LVEF < 45%;
  4. History of other malignancies within the past 5 years, excluding localized thyroid cancer and in situ skin cancer;
  5. Serum total bilirubin > 1.5 ULN (upper limit of normal); ALT or AST > 2.5 ULN; serum creatinine > 1.5 ULN;
  6. Known HIV infection;
  7. Conditions affecting the use of the study drug as assessed by the investigator;
  8. Inability to understand or comply with the study protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment arm

Induction Cycle 1 and 2: Venetoclax for 2 weeks,oral; Blinatumomab for 2weeks, iv; Dexamethasone.

Consolidation Cycle 3 and 5: Inotuzumab ozogamicin, iv. Cycle 4: Methotrexate, iv. Cycle 6: Venetoclax for 2 weeks,oral; Pegaspargase, im. Complete at least 6 intrathecal injections within 6 cycles.
Drug: Dexamethasone
Glucocorticoids
Drug: Blinatumomab
Bi-specific anti CD19/CD3 antibody
Other Names:
  • Blina
Drug: Venetoclax
BCL-2 inhibotor
Other Names:
  • Ven
Drug: Inotuzumab ozogamicin
a humanized monoclonal antibody-drug conjugate targeting CD22
Other Names:
  • INO
Drug: Methotrexate
antifolate antineoplastic drug
Other Names:
  • MTX
Drug: Pegaspargase
antitumor drug
Other Names:
  • PEG
Drug: Cytarabine
Pyrimidine, antimetabolites
Other Names:
  • Ara-C

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event free survival(EFS)
Time Frame: up to 2 years
Defined for all patients in a trial; measured from day 1 of treatment to the date of treatment failure, hematologic relapse from CR/CRi or death from any cause, whichever occurs first;
up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete remission with or without incomplete PB cell recovery(CR/CRi) rate
Time Frame: at the end of Cycle 1（each cycle is 28days）
Blast rate lower than 5% with or without peripheral blood cell recovery
at the end of Cycle 1（each cycle is 28days）
Overall survival (OS)
Time Frame: up to 5 years
Defined for all patients in a trial; measured from day 1 of treatment to the date of death from any cause;
up to 5 years
Minimal residual disease (MRD)
Time Frame: At the end of Cycle 1（each cycle is 28 days）
MRD level detected by flow cytometry which value <0.1% is defined as negtive
At the end of Cycle 1（each cycle is 28 days）

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minimal residual disease (MRD)
Time Frame: At the end of Cycle 2（each cycle is 28 days）
MRD level detected by next generation sequencing
At the end of Cycle 2（each cycle is 28 days）

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital of Zhejiang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 15, 2024

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

August 6, 2024

First Submitted That Met QC Criteria

August 14, 2024

First Posted (Actual)

August 15, 2024

Study Record Updates

Last Update Posted (Actual)

August 15, 2024

Last Update Submitted That Met QC Criteria

August 14, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT20240070C

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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