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)

Phase 1

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: 18.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864
MedDRA version: 18.0Level: LLTClassification code 10063625Term: Acute lymphoblastic leukemia recurrentSystem Organ Class: 100000004864
MedDRA version: 18.0Level: LLTClassification code 10066109Term: Precursor B-lymphoblastic leukemia acuteSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-002476-92-FR

Lead Sponsor: Amgen Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 111

Inclusion Criteria

* 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
Are the trial subjects under 18? yes
Number of subjects for this age range: 320
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

Exclusion Criteria

* 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. Abnormal serum creatinine based on age/gender
b. Direct bilirubin > 1.5 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
* Known infection with HIV
* Known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing
* 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 12 months thereafter
* 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 12 months thereafter
* 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 6 months thereafter
* Sexually mature male subject who is not willing to abstain from sperm donation while receiving protocol-required 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
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;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.;Main Objective: To evaluate event-free survival (EFS) after blinatumomab when compared to standard of care (SOC) chemotherapy.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): OS<br>MRD response<br>Incidence of adverse events (both serious and non-serious), treatment-related adverse events, adverse events of interest, clinically significant changes in laboratory values<br>Survival status at 100 days following HSCT<br>Incidence of anti-blinatumomab antibody formation (blinatumomab arm only);Timepoint(s) of evaluation of this end point: OS: from time of randomization until the end of the study, or death, whatever comes first .<br>MRD response: at the end of treatment with investigational product(s)<br>Incidence of adverse events (both serious and non-serious), treatment-related adverse events, adverse events of interest, clinically significant changes in laboratory values : during the treatment period<br>Survival status: at 100 days following alloHSCT<br> Incidence of anti-blinatumomab antibody formation (blinatumomab arm only): during the whole study

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