Blinatumomab Added to Prephase and Consolidation Therapy in Precursor B-acute Lymphoblastic Leukemia in Adults.

NCT ID: NCT03541083

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-04
• Study Completion Date: 2026-12-15

Brief 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 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.

Conditions

ALL, Adult

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Blinatumomab

Intervention Type: DRUG

prephase and consolidation (I and II)

Interventions

Blinatumomab

prephase and consolidation (I and II)

Intervention Type: DRUG

Other Intervention Names

Blincyto

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stichting Hemato-Oncologie voor Volwassenen Nederland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

A.W. Rijneveld, Dr.

Role: PRINCIPAL_INVESTIGATOR

Erasmus MC, Rotterdam

Locations

BE-Antwerpen Edegem-UZA

Antwerp, , Belgium

BE-Antwerpen-ZNASTUIVENBERG

Antwerp, , Belgium

BE-Brugge-AZBRUGGE

Bruges, , Belgium

BE-Gent-UZGENT

Ghent, , Belgium

BE-Leuven-UZLEUVEN

Leuven, , Belgium

BE-Roeselare-AZDELTA

Roeselare, , Belgium

NL-Amersfoort-MEANDERMC

Amersfoort, , Netherlands

NL-Amsterdam-AMC

Amsterdam, , Netherlands

NL-Amsterdam-VUMC

Amsterdam, , Netherlands

NL-Enschede-MST

Enschede, , Netherlands

NL-Groningen-UMCG

Groningen, , Netherlands

NL-Leiden-LUMC

Leiden, , Netherlands

NL-Maastricht-MUMC

Maastricht, , Netherlands

NL-Nieuwegein-ANTONIUS

Nieuwegein, , Netherlands

NL-Rotterdam-ERASMUSMC

Rotterdam, , Netherlands

NL-Den Haag-HAGA

The Hague, , Netherlands

NL-Utrecht-UMCUTRECHT

Utrecht, , Netherlands

NL-Zwolle-ISALA

Zwolle, , Netherlands

Countries

Belgium; Netherlands

Related Links

http://www.hovon.nl

The foundation of Hemato-Oncologie voor Volwassenen Nederland (HOVON - the Haemato Oncology Foundation for Adults in the Netherlands).

Other Identifiers

2017-000766-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HO146

Identifier Type: -

Identifier Source: org_study_id