Blinatumomab added to prephase and consolidation therapy in precursor B-acute lymphoblastic leukemia in adults.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

16 May 2018 → 11 May 2026

Decision date (initial)

2024-11-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Duch Cancer Society · Shire · Amgen

External identifiers

EU CT number

2024-511050-44-00

EudraCT number

2017-000766-30

ClinicalTrials.gov

NCT03541083

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To assess the proportion of patients that achieve MRD negative response after the first consolidation phase including blinatumomab

Secondary objectives 10

1. To assess the MRD level following induction chemotherapy
2. To assess the MRD level after second blinatumomab consolidation
3. To assess the hematological response after induction, blinatumomab consolidation I and blinatumomab consolidation II
4. To evaluate event-free survival (EFS)
5. To evaluate relapse-free survival (RFS)
6. To evaluate overall survival (OS)
7. To evaluate safety and toxicity of blinatumomab
8. To assess clinical outcome of patients receiving maintenance or allogeneic SCT
9. To assess kinetics of T-cells and B-cells and their various subsets during treatment and assess their predictive value as regard to molecular response
10. To compare the results of molecular and flowcytometric MRD measurements at the same timepoints

Conditions and MedDRA coding

Precursor B-acute lymphoblastic leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Primary CD19 positive precursor B-ALL (excluding mature B-cell ALL and B-lymphoblastic lymphoma, but including Philadelphia positive/BCR-ABL positive ALL) and CD19 positive mixed phenotype acute lymphoblastic leukemia (MPAL)
2. Patients aged 18 to 70 years inclusive
3. WHO performance status 0-2
4. Negative pregnancy test at inclusion, if applicable
5. Written informed consent
6. Patient is capable of giving informed consent

Exclusion criteria 16

1. Mature B-cell leukemia/lymphoma, B-lymphoblastic lymphoma, isolated extramedullary disease
2. CML in blast crisis
3. Acute undifferentiated leukemia
4. Previous treatment with chemotherapy for precursor B-ALL (maximum 5 days of steroid treatment is allowed)
5. Persistent liver enzyme disorders (ASAT/ALAT) >5xULN despite steroid pre-treatment
6. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease)
7. Severe pulmonary dysfunction (CTCAE grade III-IV)
8. Severe neurological or psychiatric disease
9. Active, uncontrolled infection
10. Patients with a currently active second malignancy. Patients are not considered to have a currently active malignancy if they have completed therapy and are considered by their physician to be at < 30% risk of relapse within one year. However, patients with the following history/concurrent conditions are allowed: - Basal or squamous cell carcinoma of the skin, - Carcinoma in situ of the cervix, - Carcinoma in situ of the breast, - Incidental histologic finding of prostate carcinoma
11. Patient known to be HIV-positive
12. Pregnant or breast-feeding female patients
13. 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)
14. Current participation in another clinical trial
15. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
16. Clinically overt central nervous system disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of MRD negative response by PCR/FCM after the first blinatumomab consolidation course. MRD negative response is defined as MRD <10^-4 by PCR or FCM

Secondary endpoints 10

1. MRD level following induction chemotherapy
2. MRD level after second blinatumomab consolidation
3. Hematological response after induction, blinatumomab consolidation I and blinatumomab consolidation II
4. Event-free survival, i.e. time from registration until no CR on protocol, relapse or death from any cause, whichever comes first. EFS for patients without a CR on protocol will be set at 1 day; this also includes patients with a first CR only after start intensification 1. Patients still in first CR and alive are censored at the last day they were last known to be alive.
5. Relapse-free survival (hematologically; i.e. time from CR on protocol until relapse or death from any cause, whichever comes first). Patients still in first CR and alive are censored at the last day they were last known to be alive.
6. Overall survival, measured from the time of registration until death from any cause. Patients still alive or lost to follow up are censored at the date they were last known to be alive.
7. Adverse events
8. RFS and OS from start allogeneic transplantation and from start maintenance RFS, whichever is applicable
9. T-cell and B-cell kinetics and assessment of predictive value
10. Comparison of the results of molecular and flowcytometric MRD measurements at the same timepoints (sidestudy)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Sponsor organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Contact name

A.W. Rijneveld

Public contact point

Organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Contact name

M.C. Breems - de Ridder

Third parties 2

Locations

2 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications