- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03541083
Blinatumomab Added to Prephase and Consolidation Therapy in Precursor B-acute Lymphoblastic Leukemia in Adults. (HOVON146ALL)
July 12, 2023 updated by: Stichting Hemato-Oncologie voor Volwassenen Nederland
Blinatumomab Added to Prephase and Consolidation Therapy in Precursor B-acute Lymphoblastic Leukemia in Adults. A Phase II Trial
Blinatumomab is a new active bispecific monoclonal antibody for treatment of lymphoid malignancies, including ALL (acute Lymphoblastic Leukemia ) whose activity for remission induction needs to be explored in combination with standardized treatment in order to improve outcome of this disease which is still lethal in most adult patients.
Ultimate proof of efficacy resides in an increase of reaching MRD ( minimal residual disease) negativity, prolongation of that response, and long-term survival.
Since hematological response rate in adult ALL is high already and defining long-term survival in a large clinical trial takes many years, this trial aims to improve the strength of the MRD response as defined by achieving complete MRD negative response (ie, < 10^-4) after the first consolidation phase including blinatumomab.
This MRD response will be assessed by Real-Time Quantitative Polymerase Chain Reaction (RQ-PCR) analysis of patient-specific Ig/TCR (T-cell receptor ) gene rearrangements.
When MRD data are missing, MRD positivity will be assumed.
Although younger (up to 40 years of age) patients are treated more intensively than older patients (older than 40 years of age), the investigational questions concerning blinatumomab can be examined in both subgroups as both younger and older patients receive the same type of chemotherapy courses with dose adjustments for chemotherapeutic agents only for patients above 60 years of age.
Study Overview
Detailed Description
This trial aims to improve the strength of the MRD ( minimal residual disease) response as defined by achieving complete MRD negative response (ie, < 10^-4) after the first consolidation phase including blinatumomab.
Study Type
Interventional
Enrollment (Actual)
71
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 Locations
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Antwerpen, Belgium
- BE-Antwerpen-ZNASTUIVENBERG
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Antwerpen, Belgium
- BE-Antwerpen Edegem-UZA
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Brugge, Belgium
- BE-Brugge-AZBRUGGE
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Gent, Belgium
- BE-Gent-UZGENT
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Leuven, Belgium
- BE-Leuven-UZLEUVEN
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Roeselare, Belgium
- BE-Roeselare-AZDELTA
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Amersfoort, Netherlands
- NL-Amersfoort-MEANDERMC
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Amsterdam, Netherlands
- NL-Amsterdam-AMC
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Amsterdam, Netherlands
- NL-Amsterdam-VUMC
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Den Haag, Netherlands
- NL-Den Haag-HAGA
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Enschede, Netherlands
- NL-Enschede-MST
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Groningen, Netherlands
- NL-Groningen-UMCG
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Leiden, Netherlands
- NL-Leiden-LUMC
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Maastricht, Netherlands
- NL-Maastricht-MUMC
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Nieuwegein, Netherlands
- NL-Nieuwegein-ANTONIUS
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Rotterdam, Netherlands
- NL-Rotterdam-ERASMUSMC
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Utrecht, Netherlands
- NL-Utrecht-UMCUTRECHT
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Zwolle, Netherlands
- NL-Zwolle-ISALA
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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
16 years to 68 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Primary CD19 (cluster of differentiation antigen 19) positive precursor B-ALL (excluding mature B-cell ALL and B-lymphoblastic lymphoma, but including Philadelphia positive/BCR-ABL (Abelson murine leukemia viral oncogene homolog 1) positive ALL) and CD19 positive mixed phenotype acute lymphoblastic leukemia (MPAL);
- Patients aged 18 to 70 years inclusive;
- WHO ( World Health Organization) performance status 0-2;
- Negative pregnancy test at inclusion, if applicable;
- Written informed consent;
- Patient is capable of giving informed consent.
Exclusion Criteria:
- Mature B-cell leukemia/lymphoma, B-lymphoblastic lymphoma, isolated extramedullary disease;
- CML (Chronic myeloid leukemia) in blast crisis;
- Acute undifferentiated leukemia;
- Previous treatment with chemotherapy for precursor B-ALL (maximum 5 days of steroid treatment is allowed)
- Persistent liver enzyme disorders (ASAT/ALAT) >5xULN (Upper Limit of Normal) despite steroid pre-treatment (see also 8.1.3.)
- Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease);
- Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D);
- Severe neurological or psychiatric disease;
- Active, uncontrolled infection;
- Clinically overt central nervous system disease;
- History of active malignancy during the past 5 years with the exception of basal cell carcinoma of the skin or stage 0 cervical carcinoma;
- Patient known to be HIV-positive;
- Pregnant or breast-feeding female patients;
- Unwilling or not capable to use effective means of birth control (all men, all premenopausal women under the age of 50 need contraception for two years after the last period, and women older than 50 years for at least one year);
- Current participation in another clinical trial;
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
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 |
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Experimental: Blinatumomab
After a 5-day steroid prephase patients will receive two weeks continuous infusion of blinatumomab.
Then the first remission-induction course will be given after one week interruption.
Subsequent therapy with 4 cycles of chemotherapy and two 4-week courses of blinatumomab will follow, and subsequently depending on risk group, eligibility and a suitable donor either allogeneic stem cell transplantation or 2 year maintenance treatment.
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prephase and consolidation (I and II)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The proportion of patients that achieve MRD ( minimal residual disease) negative response, measured by Polymerase Chain Reaction (PCR), after the first blinatumomab consolidation course. MRD negative response is defined as MRD <10-4
Time Frame: 1 year after closure of study
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1 year after closure of study
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Complete and molecular response rate following induction and after blinatumomab consolidation ll by the addition of i.v. blinatumomab to standard prophase, consolidation and intensification therapy
Time Frame: 1 year after closure of study
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1 year after closure of study
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Event-free survival (EFS)
Time Frame: 1 year after closure of study
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1 year after closure of study
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Relapse-free survival (RFS)
Time Frame: 1 year after closure of study
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1 year after closure of study
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Overall survival (OS)
Time Frame: 1 year after closure of study
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1 year after closure of study
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Adverse events; assessing the safety and toxicity of adding blinatumomab to standard prophase and consolidation therapy (two times) in adult ALL
Time Frame: 1 year after closure of study
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1 year after closure of study
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RFS and OS from start allogeneic transplantation and from start maintenance RFS
Time Frame: 1 year after closure of study
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1 year after closure of study
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Comparison of molecular and flowcytometric MRD measurements at the same timepoints
Time Frame: 1 year after closure of study
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1 year after closure of study
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: A.W. Rijneveld, Dr., Erasmus MC, Rotterdam
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.
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 (Actual)
June 4, 2018
Primary Completion (Actual)
November 30, 2020
Study Completion (Estimated)
December 15, 2026
Study Registration Dates
First Submitted
March 20, 2018
First Submitted That Met QC Criteria
May 29, 2018
First Posted (Actual)
May 30, 2018
Study Record Updates
Last Update Posted (Actual)
July 13, 2023
Last Update Submitted That Met QC Criteria
July 12, 2023
Last Verified
July 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HO146
- 2017-000766-30 (EudraCT Number)
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
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
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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