Clinical Study to Investigate the Efficacy, Safety, and Tolerability of the bispecific antibody Blinatumomab as Consolidation Therapy Versus Conventional Consolidation Chemotherapy in Pediatric Subjects with High-risk First Relapse Acute Lymphoblastic Leukemia (ALL)
- Conditions
- Patients with Philadelphia chromosome negative (Ph-) high-risk (HR) first relapse B-precursor ALL (as defined by I-BFM SG/IntReALL criteria)MedDRA version: 20.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10063625Term: Acute lymphoblastic leukemia recurrentSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10066109Term: Precursor B-lymphoblastic leukemia acuteSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-002476-92-CZ
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 320
* 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 (< 25% leukemic cells by cytomorphology) 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).
Are the trial subjects under 18? yes
Number of subjects for this age range: 202
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
* 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 in the 20120215 protocol
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). 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 female subject who is pregnant or breastfeeding, or is
planning to become pregnant or breastfeed while receiving protocolspecified
therapy and for at least 6 months 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
sexual abstinence or use a highly effective form of contraception while
receiving protocol-specified therapy and for at least 6 months 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 sexual
abstinence or use a condom with spermicide while receiving protocolspecified
therapy and for at least 6 months thereafter. In countries
where spermicide is not available, a condom without spermicide is
acceptable.
* Sexually mature male subject who is not willing to abstain from sperm
donation while receiving protocol-specified therapy and for at least 6
months thereafter
* Subject likely to not be available to complete all protocol-required
study visits or procedures, including follow-up visits, and/or to comply
with all required study procedures to the best of the subject's and
investigator's knowledge
* History or evidence of any other clinically significant disorder,
condition or disease (with the exception of those outlined above) that, in
the opinion of the investigator or Amgen physician, if consulted, would
pose a risk to subject safety or interfere with the study evaluation,
procedures, or completion.
* Placed into an institution due to juridical or regulatory ruling
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate event-free survival (EFS) after blinatumomab when compared to standard of care (SOC) chemotherapy.;Primary end point(s): EFS;Timepoint(s) of evaluation of this end point: from the time of randomization until the date of relapse or M2 marrow after having achieved a CR, failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first.;Secondary Objective: To evaluate the effect of blinatumomab on overall survival (OS) when compared to SOC chemotherapy<br>• To evaluate reduction in minimal residual disease (MRD) after blinatumomab when compared to SOC chemotherapy<br>• To evaluate the safety of blinatumomab when compared to SOC chemotherapy<br>• To evaluate the safety of allogeneic hematopoietic stem cell transplantation (alloHSCT) after blinatumomab when compared to alloHSCT after SOC chemotherapy<br>•To evaluate the pharmacokinetics (PK) of Blinatumomab
- Secondary Outcome Measures
Name Time Method