A Randomized, Open-label, Controlled Phase 3 Trial to Investigate the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab as Consolidation Therapy Versus Conventional Consolidation Chemotherapy in Pediatric Subjects with High-risk First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)
- Conditions
- acute lymphoblastic leukemia (ALL)leukemia10024324
- Registration Number
- NL-OMON53052
- Lead Sponsor
- Amgen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
* Subjects with Philadelphia (Ph-) chromosome negative high-risk (HR) first
relapse B-precursor ALL (as defined by I-BFM SG/IntReALL criteria), * Subjects
with M1 or M2 marrow at the time of randomization , * Age > 28 days and <18
years at the time of informed consent/assent, * Subject*s legally acceptable
representative has provided informed consent when the subject is legally too
young to provide informed consent and the subject has provided written assent
based on local regulations and/or guidelines prior to any study-specific
activities/procedures being initiated
* Availability of the following material from relapse diagnosis for central
analysis of MRD by PCR: clone-specific primers and reference DNA, as well as
primer sequences and analyzed sequences of clonal rearrangements (cases with
isolated extramedullary relapse or cases with technical and/or logistic hurdles
to obtain and process bone marrow material are exempt from providing this
material. In these cases, central MRD analysis only by Flow is permitted).)
* Clinically relevant CNS pathology requiring treatment (eg, unstable
epilepsy) Evidence of current CNS (CNS 2, CNS 3) involvement by ALL. Subjects
with CNS relapse at the time of relapse are eligible if CNS is successfully
treated prior to enrollment., * Abnormal renal or hepatic function prior to
start of treatment (day 1) as defined below:
a. Serum creatinine levels above upper limit of normal, based on the normal
ranges for age and gender of the local laboratories
b. Total bilirubin > 3.0 mg/dL prior to start of treatment (unless related to
Gilbert*s or Meulengracht disease)
* Peripheral neutrophils < 500/µl prior to start of treatment,
* Peripheral platelets < 50,000/µl prior to start of treatment,
* Currently receiving treatment in another investigational device or drug
study, or less than 4 weeks since ending treatment on another investigational
device or drug study(s). Other investigational procedures while participating
in this study are excluded. Procedures required by IntReALL HR guidelines are
allowed.,
* Chemotherapy related toxicities that have not resolved to <= grade 2 ,
* Symptoms and/or clinical signs and/or radiological and/or sonographic signs
that indicate an acute or uncontrolled chronic infection, any other concurrent
disease or medical condition that could be exacerbated by the treatment or
would seriously complicate compliance with the protocol,
* documented infection with HIV,
* Known hypersensitivity to immunoglobulins or any of the products or
components to be administered during dosing (excluding asparaginase),
* Post-menarchal subject who is pregnant or breastfeeding, or is planning to
become pregnant or breastfeed while receiving protocol-required therapy and for
at least 48 hours after the last dose of blinatumomab, or 12 months after the
last dose of chemotherapy
* Post-menarchal female subject who is not willing to practice true abstinence
or use a highly effective form of contraception while receiving
protocol-required therapy and for at least 48 hours after the last dose of
blinatumomab, or 12 months after the last dose of chemotherapy
* Sexually mature male subject who is not willing to practice true abstinence
or use a condom while receiving protocol-required therapy and for at least 48
hours thereafter ,
* Sexually mature male subject who is not willing to abstain from sperm
donation while receiving protocol-required therapy and for at least 48 hours
thereafter
Refer to section 4.2 of the protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>• EFS</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>• OS<br /><br>• MRD response, defined as MRD level < 10-4 at the end of treatment with<br /><br>investigational<br /><br>product(s)<br /><br>• Incidence of adverse events (both serious and non-serious), treatment-related<br /><br>adverse<br /><br>events, adverse events of interest, clinically significant changes in<br /><br>laboratory values<br /><br>• Survival status at 100 days following alloHSCT<br /><br>• Incidence of anti-blinatumomab antibody formation (blinatumomab arm only)<br /><br>• population pharmacokinetic (PK) analysis</p><br>