Clinical trial NCT03541083: Blinatumomab Added to Prephase and Consolidation Therapy in Precursor B-acute Lymphoblastic Leukemia in Adults.
Official title: Blinatumomab Added to Prephase and Consolidation Therapy in Precursor B-acute Lymphoblastic Leukemia in Adults. A Phase II Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: ALL, Adult
Lead sponsor: Stichting Hemato-Oncologie voor Volwassenen Nederland
Sponsor class: OTHER
First posted: 2018-05-30
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
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
timeFrame: 1 year after closure of study
Secondary outcomes:
measure: 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
timeFrame: 1 year after closure of study
measure: Event-free survival (EFS)
timeFrame: 1 year after closure of study
measure: Relapse-free survival (RFS)
timeFrame: 1 year after closure of study
measure: Overall survival (OS)
timeFrame: 1 year after closure of study
measure: Adverse events; assessing the safety and toxicity of adding blinatumomab to standard prophase and consolidation therapy (two times) in adult ALL
timeFrame: 1 year after closure of study
measure: RFS and OS from start allogeneic transplantation and from start maintenance RFS
timeFrame: 1 year after closure of study
measure: Comparison of molecular and flowcytometric MRD measurements at the same timepoints
timeFrame: 1 year after closure of study
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: BE-Antwerpen Edegem-UZA
city: Antwerpen
country: Belgium
facility: BE-Antwerpen-ZNASTUIVENBERG
city: Brugge
country: Belgium
facility: BE-Brugge-AZBRUGGE
city: Gent
country: Belgium
facility: BE-Gent-UZGENT
city: Leuven
country: Belgium
facility: BE-Leuven-UZLEUVEN
city: Roeselare
country: Belgium
facility: BE-Roeselare-AZDELTA
city: Amersfoort
country: Netherlands
facility: NL-Amersfoort-MEANDERMC
city: Amsterdam
country: Netherlands
facility: NL-Amsterdam-AMC
city: Amsterdam
country: Netherlands
facility: NL-Amsterdam-VUMC
city: Den Haag
country: Netherlands
facility: NL-Den Haag-HAGA
city: Enschede
country: Netherlands
facility: NL-Enschede-MST
city: Groningen
country: Netherlands
facility: NL-Groningen-UMCG
city: Leiden
country: Netherlands
facility: NL-Leiden-LUMC
city: Maastricht
country: Netherlands
facility: NL-Maastricht-MUMC
city: Nieuwegein
country: Netherlands
facility: NL-Nieuwegein-ANTONIUS
city: Rotterdam
country: Netherlands
facility: NL-Rotterdam-ERASMUSMC
city: Utrecht
country: Netherlands
facility: NL-Utrecht-UMCUTRECHT
city: Zwolle
country: Netherlands
facility: NL-Zwolle-ISALA
Study officials:
affiliation: Erasmus MC, Rotterdam
name: A.W. Rijneveld, Dr.
role: PRINCIPAL_INVESTIGATOR
References: