This study has been transitioned to CTIS with ID 2024-511050-44-00 check the CTIS register for the current data. Primary objective:-To assess the proportion of patients that achieve MRD negative response (by PCR/FCM) after the first consolidation…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of MRD negative response by PCR/FCM after the first blinatumomab
consolidation course. MRD negative response is defined as MRD <10^-4.
Secondary outcome
-MRD level following induction chemotherapy
-MRD level after second blinatumomab consolidation
-Hematological response after induction, blinatumomab consolidation I and
blinatumomab consolidation II
-Event free survival, i.e. time from registration until no CR on protocol
(i.e. after prephase, induction, consolidation I, or blinatumomab after
consolidation I), 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.
-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.
-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.
-Adverse events
-RFS and OS from start allogeneic transplantation and from start maintenance
RFS, whichever is applicable
-T-cell and B-cell kinetics and assessment of predictive value
-Comparison of the results of molecular and flowcytometric MRD measurements at
the same timepoints (sidestudy)
Background summary
Blinatumomab is a new active bispecific monoclonal antibody for treatment of
lymphoid malignancies, including ALL 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 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 RQ-PCR analysis of patient-specific Ig/TCR 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.
Study objective
This study has been transitioned to CTIS with ID 2024-511050-44-00 check the CTIS register for the current data.
Primary objective:
-To assess the proportion of patients that achieve MRD negative response (by
PCR/FCM) after the first consolidation phase including blinatumomab.
Secondary objectives:
-To assess the MRD level following induction chemotherapy
-To assess the MRD level after second blinatumomab consolidation
-To assess the hematological response after induction, blinatumomab
consolidation I and blinatumomab consolidation II
-To evaluate event-free survival (EFS)
-To evaluate relapse-free survival (RFS)
-To evaluate overall survival (OS)
-To document safety and toxicity of blinatumomab
-To assess clinical outcome of patients receiving maintenance or allogeneic SCT
-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
-To compare the results of molecular and flowcytometric MRD measurements at the
same timepoints.
Study design
A prospective, single arm, phase II study in which i.v. blinatumomab is added
to standard prephase and subsequent therapy.
Intervention
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.
Study burden and risks
Longer period of treatment and a potential cytokine release syndrome (<5%) and
neurological complications which are mostly completely reversible.
VUMC, HOVON Centraal Bureau, De Boelelaan 1117
Amsterdam 1081 HV
NL
VUMC, HOVON Centraal Bureau, De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- 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);
- Patients aged 18 to 70 years inclusive;
- WHO 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 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 despite steroid
pre-treatment;
- Severe cardiovascular disease (arrhythmias requiring chronic treatment,
congestive heart failure or symptomatic ischemic heart disease);
- Severe pulmonary dysfunction (CTCAE grade III-IV);
- Severe neurological or psychiatric disease;
- Active, uncontrolled infection;
- Clinically overt central nervous system disease;
- 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:
o Basal or squamous cell carcinoma of the skin
o Carcinoma in situ of the cervix
o Carcinoma in situ of the breast
o Incidental histologic finding of prostate 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-511050-44-00 |
| EudraCT | EUCTR2017-000766-30-NL |
| ClinicalTrials.gov | NCT03541083 |
| CCMO | NL61022.078.17 |