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

Primary Purpose

ALL, Adult

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Blinatumomab
Sponsored by
Stichting Hemato-Oncologie voor Volwassenen Nederland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ALL, Adult

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • BE-Antwerpen Edegem-UZA
  • BE-Antwerpen-ZNASTUIVENBERG
  • BE-Brugge-AZBRUGGE
  • BE-Gent-UZGENT
  • BE-Leuven-UZLEUVEN
  • BE-Roeselare-AZDELTA
  • NL-Amersfoort-MEANDERMC
  • NL-Amsterdam-AMC
  • NL-Amsterdam-VUMC
  • NL-Den Haag-HAGA
  • NL-Enschede-MST
  • NL-Groningen-UMCG
  • NL-Leiden-LUMC
  • NL-Maastricht-MUMC
  • NL-Nieuwegein-ANTONIUS
  • NL-Rotterdam-ERASMUSMC
  • NL-Utrecht-UMCUTRECHT
  • NL-Zwolle-ISALA

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Blinatumomab

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Event-free survival (EFS)
Relapse-free survival (RFS)
Overall survival (OS)
Adverse events; assessing the safety and toxicity of adding blinatumomab to standard prophase and consolidation therapy (two times) in adult ALL
RFS and OS from start allogeneic transplantation and from start maintenance RFS
Comparison of molecular and flowcytometric MRD measurements at the same timepoints

Full Information

First Posted
March 20, 2018
Last Updated
July 12, 2023
Sponsor
Stichting Hemato-Oncologie voor Volwassenen Nederland
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1. Study Identification

Unique Protocol Identification Number
NCT03541083
Brief Title
Blinatumomab Added to Prephase and Consolidation Therapy in Precursor B-acute Lymphoblastic Leukemia in Adults.
Acronym
HOVON146ALL
Official Title
Blinatumomab Added to Prephase and Consolidation Therapy in Precursor B-acute Lymphoblastic Leukemia in Adults. A Phase II Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 4, 2018 (Actual)
Primary Completion Date
November 30, 2020 (Actual)
Study Completion Date
December 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stichting Hemato-Oncologie voor Volwassenen Nederland

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ALL, Adult

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
71 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Blinatumomab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Blinatumomab
Other Intervention Name(s)
Blincyto
Intervention Description
prephase and consolidation (I and II)
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
Event-free survival (EFS)
Time Frame
1 year after closure of study
Title
Relapse-free survival (RFS)
Time Frame
1 year after closure of study
Title
Overall survival (OS)
Time Frame
1 year after closure of study
Title
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
Title
RFS and OS from start allogeneic transplantation and from start maintenance RFS
Time Frame
1 year after closure of study
Title
Comparison of molecular and flowcytometric MRD measurements at the same timepoints
Time Frame
1 year after closure of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
A.W. Rijneveld, Dr.
Organizational Affiliation
Erasmus MC, Rotterdam
Official's Role
Principal Investigator
Facility Information:
Facility Name
BE-Antwerpen Edegem-UZA
City
Antwerpen
Country
Belgium
Facility Name
BE-Antwerpen-ZNASTUIVENBERG
City
Antwerpen
Country
Belgium
Facility Name
BE-Brugge-AZBRUGGE
City
Brugge
Country
Belgium
Facility Name
BE-Gent-UZGENT
City
Gent
Country
Belgium
Facility Name
BE-Leuven-UZLEUVEN
City
Leuven
Country
Belgium
Facility Name
BE-Roeselare-AZDELTA
City
Roeselare
Country
Belgium
Facility Name
NL-Amersfoort-MEANDERMC
City
Amersfoort
Country
Netherlands
Facility Name
NL-Amsterdam-AMC
City
Amsterdam
Country
Netherlands
Facility Name
NL-Amsterdam-VUMC
City
Amsterdam
Country
Netherlands
Facility Name
NL-Den Haag-HAGA
City
Den Haag
Country
Netherlands
Facility Name
NL-Enschede-MST
City
Enschede
Country
Netherlands
Facility Name
NL-Groningen-UMCG
City
Groningen
Country
Netherlands
Facility Name
NL-Leiden-LUMC
City
Leiden
Country
Netherlands
Facility Name
NL-Maastricht-MUMC
City
Maastricht
Country
Netherlands
Facility Name
NL-Nieuwegein-ANTONIUS
City
Nieuwegein
Country
Netherlands
Facility Name
NL-Rotterdam-ERASMUSMC
City
Rotterdam
Country
Netherlands
Facility Name
NL-Utrecht-UMCUTRECHT
City
Utrecht
Country
Netherlands
Facility Name
NL-Zwolle-ISALA
City
Zwolle
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.hovon.nl
Description
The foundation of Hemato-Oncologie voor Volwassenen Nederland (HOVON - the Haemato Oncology Foundation for Adults in the Netherlands).

Learn more about this trial

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

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