HOVON146ALL: Blinatumomab Added to Prephase and Consolidation Therapy in Precursor B-acute Lymphoblastic Leukemia in Adults.

Sponsor
Stichting Hemato-Oncologie voor Volwassenen Nederland (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03541083
Collaborator
(none)
71
18
1
102.4
3.9
0

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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

Study Type:
Interventional
Actual Enrollment :
71 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Blinatumomab Added to Prephase and Consolidation Therapy in Precursor B-acute Lymphoblastic Leukemia in Adults. A Phase II Trial
Actual Study Start Date :
Jun 4, 2018
Anticipated Primary Completion Date :
Mar 30, 2022
Anticipated Study Completion Date :
Dec 15, 2026

Arms and Interventions

Arm Intervention/Treatment
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.

Drug: Blinatumomab
prephase and consolidation (I and II)
Other Names:
  • Blincyto
  • Outcome Measures

    Primary Outcome Measures

    1. 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 [1 year after closure of study]

    Secondary Outcome Measures

    1. 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 [1 year after closure of study]

    2. Event-free survival (EFS) [1 year after closure of study]

    3. Relapse-free survival (RFS) [1 year after closure of study]

    4. Overall survival (OS) [1 year after closure of study]

    5. Adverse events; assessing the safety and toxicity of adding blinatumomab to standard prophase and consolidation therapy (two times) in adult ALL [1 year after closure of study]

    6. RFS and OS from start allogeneic transplantation and from start maintenance RFS [1 year after closure of study]

    7. Comparison of molecular and flowcytometric MRD measurements at the same timepoints [1 year after closure of study]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 BE-Antwerpen Edegem-UZA Antwerpen Belgium
    2 BE-Antwerpen-ZNASTUIVENBERG Antwerpen Belgium
    3 BE-Brugge-AZBRUGGE Brugge Belgium
    4 BE-Gent-UZGENT Gent Belgium
    5 BE-Leuven-UZLEUVEN Leuven Belgium
    6 BE-Roeselare-AZDELTA Roeselare Belgium
    7 NL-Amersfoort-MEANDERMC Amersfoort Netherlands
    8 NL-Amsterdam-AMC Amsterdam Netherlands
    9 NL-Amsterdam-VUMC Amsterdam Netherlands
    10 NL-Den Haag-HAGA Den Haag Netherlands
    11 NL-Enschede-MST Enschede Netherlands
    12 NL-Groningen-UMCG Groningen Netherlands
    13 NL-Leiden-LUMC Leiden Netherlands
    14 NL-Maastricht-MUMC Maastricht Netherlands
    15 NL-Nieuwegein-ANTONIUS Nieuwegein Netherlands
    16 NL-Rotterdam-ERASMUSMC Rotterdam Netherlands
    17 NL-Utrecht-UMCUTRECHT Utrecht Netherlands
    18 NL-Zwolle-ISALA Zwolle Netherlands

    Sponsors and Collaborators

    • Stichting Hemato-Oncologie voor Volwassenen Nederland

    Investigators

    • Principal Investigator: A.W. Rijneveld, Dr., Erasmus MC, Rotterdam

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Stichting Hemato-Oncologie voor Volwassenen Nederland
    ClinicalTrials.gov Identifier:
    NCT03541083
    Other Study ID Numbers:
    • HO146
    • 2017-000766-30
    First Posted:
    May 30, 2018
    Last Update Posted:
    Dec 30, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 30, 2021