ALL, AdultPhase 2HOVON146ALLNCT03541083
Blinatumomab Added to Prephase and Consolidation Therapy in Precursor B-acute Lymphoblastic Leukemia in Adults.
A Phase 2 study testing Blinatumomab in people with ALL, Adult, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 18 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- ALL, Adult
- What is being tested?
- Blinatumomab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 18 sitesin 2 countries
- Study dates
- 4 Jun 2018to 15 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
18 sites in 2 countries.
18 sites in 2 countries
Netherlands12 sites
NL-Amersfoort-MEANDERMC
Amersfoort
NL-Amsterdam-AMC
Amsterdam
NL-Amsterdam-VUMC
Amsterdam
NL-Enschede-MST
Enschede
NL-Groningen-UMCG
Groningen
NL-Leiden-LUMC
Leiden
NL-Maastricht-MUMC
Maastricht
NL-Nieuwegein-ANTONIUS
Nieuwegein
NL-Rotterdam-ERASMUSMC
Rotterdam
NL-Den Haag-HAGA
The Hague
NL-Utrecht-UMCUTRECHT
Utrecht
NL-Zwolle-ISALA
Zwolle
Belgium6 sites
BE-Antwerpen Edegem-UZA
Antwerp
BE-Antwerpen-ZNASTUIVENBERG
Antwerp
BE-Brugge-AZBRUGGE
Bruges
BE-Gent-UZGENT
Ghent
BE-Leuven-UZLEUVEN
Leuven
BE-Roeselare-AZDELTA
Roeselare
About this study
Official title: 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.
Read the 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.
- Conditions
- ALL, Adult
- Being tested
- Blinatumomab
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BlinatumomabDrug
Also called Blincyto
prephase and consolidation (I and II)
| Study group | Role | What they receive |
|---|---|---|
| Blinatumomab | Experimental | 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. Receives: Drug: Blinatumomab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 year after closure of study
Secondary outcomes (7)
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
Measured: 1 year after closure of study
Event-free survival (EFS)
Measured: 1 year after closure of study
Relapse-free survival (RFS)
Measured: 1 year after closure of study
Overall survival (OS)
Measured: 1 year after closure of study
Adverse events; assessing the safety and toxicity of adding blinatumomab to standard prophase and consolidation therapy (two times) in adult ALL
Measured: 1 year after closure of study
RFS and OS from start allogeneic transplantation and from start maintenance RFS
Measured: 1 year after closure of study
Comparison of molecular and flowcytometric MRD measurements at the same timepoints
Measured: 1 year after closure of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2018
- Study start4 Jun 2018
- Primary completion30 Nov 2020
- Study completion15 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALL, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stichting Hemato-Oncologie voor Volwassenen Nederland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- A.W. Rijneveld, Dr., Principal investigator, Erasmus MC, Rotterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03541083
- Sponsor's protocol ID
- HO146
- Other IDs
- 2017-000766-30, 2017
- Acronym
- HOVON146ALL
- Status last verified
- Sep 2024
- First submitted
- 20 Mar 2018
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blinatumomab Added to Prephase and Consolidation Therapy in Precursor B-acute Lymphoblastic Leukemia in Adults. A Phase II Trial
- ClinicalTrials.gov ID
- NCT03541083
- Acronym / sponsor ID
- HOVON146ALL / HO146
- Conditions
- ALL, Adult
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Stichting Hemato-Oncologie voor Volwassenen NederlandUniversity, hospital or other
- Study start
- 4 Jun 2018 (actual)
- Primary completion
- 30 Nov 2020 (actual)
- Study completion
- 15 Dec 2026 (estimated)
- First posted
- 30 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Blinatumomab | Experimental | Drug: BlinatumomabAfter 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (16 listed)
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BlinatumomabAlso: Blincytoprephase and consolidation (I and II) | Drug | Blinatumomab |
Primary outcome
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
7 secondary outcomes
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
Event-free survival (EFS)
Time frame: 1 year after closure of study
Relapse-free survival (RFS)
Time frame: 1 year after closure of study
Overall survival (OS)
Time frame: 1 year after closure of study
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
RFS and OS from start allogeneic transplantation and from start maintenance RFS
Time frame: 1 year after closure of study
Comparison of molecular and flowcytometric MRD measurements at the same timepoints
Time frame: 1 year after closure of study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- The foundation of Hemato-Oncologie voor Volwassenen Nederland (HOVON - the Haemato Oncology Foundation for Adults in the Netherlands).Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
A.W. Rijneveld, Dr. principal investigator
Erasmus MC, Rotterdam
18 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Blinatumomab in people with ALL, Adult, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 18 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Netherlands, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.