AMG20130320

Principal Investigator: Phillip Barnette
Keywords: Pediatric , Oncology , Relapsed Leukemia , Relapsed B-cell Leukemia Department: Pediatric Administration
IRB Number: 00076435 Co Investigator:  
Specialty: Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Jennifer Craig
jennifer.craig@imail.org
8016624715

Brief Summary

Primary Objective:

To estimate the incidence of treatment-emergent and treatment-related adverse events during

treatment with blinatumomab in pediatric and adolescent subjects with B-precursor ALL in second

or later bone marrow relapse, in any marrow relapse after alloHSCT, or refractory to other

treatments

Secondary Objective(s):

To describe key efficacy outcomes, including incidence of complete response (CR) within

2 cycles of blinatumomab, minimal residual disease (MRD) remission within 2 cycles of

blinatumomab, relapse free survival (RFS), overall survival (OS), incidence of alloHSCT, and

100-day mortality after alloHSCT.

Hypotheses:

A formal statistical hypothesis will not be tested. The incidence of treatment-emergent and

treatment-related adverse events will be estimated.

Study Endpoints:

Incidence of treatment-emergent and treatment-related adverse events

Incidence of Complete remission within 2 cycles of blinatumomab

•Minimal Residual Disease remission within 2 cycles of blinatumomab

Relapse Free Survival

Overall Survival

Incidence of alloHematopoietic Stem Cell Transplant (HSCT)

100-day mortality after alloHSCT

Inclusion Criteria

Inclusion Criteria

Immunophenotypic evidence of CD19 postive B-precursor ALL (pro B-, pre B-, common ALL)

Age > 28 days and < 18 years at the time of informed consent/assent

Morphological evidence of relapsed/refractory disease, defined as one of the following:

  •    Second or later bone marrow relapse (defined as M3 marrow or M2 marrow or M1 marrow but with an MRD level less than or equal to 10^-3), or

Any marrow relapse after alloHSCT (defined as M3 marrow or M2 marrow or M1 marrow but with an MRD level of less than or equal to 10^-3), or

Refractory to other treatments:

o For patients in first relapse: failure to achieve a CR following a full standard reinduction chemotherapy regimen

o For patients who have not achieved a first remission: failure to achieve remission following a full standard induction regimen

Subjects previously treated with blinatumomab may be eligible, if subject ended treatment for reason(s) other than disease progression or intolerability to blinatumomab

Karnofsky performance status 50% for patients 16 years and Lansky performance status of 50% for patients < 16 years

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

Subject does not qualify for or cannot access other comparable or satisfactory alternative therapy for CD19 positive B-precursor ALL

Adequate liver function defined as:

ALT (SGPT) 135 IU/L at least once during screening

Exclusion Criteria

  • Any active acute Graft-versus-Host Disease (GvHD) grade 2 to grade 4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment
  • Immunosuppressive agents to prevent or treat GvHD within 2 weeks prior to blinatumomab treatment (except for topical corticosteroids)
  • Active (overt) ALL in the CNS (confirmed by cerebrospinal fluid [CSF] analysis) or in testes
  • History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis

- With the exception of CNS leukemia that is well controlled with intrathecal therapy

  • Current autoimmune disease or history of autoimmune disease with potentialCNS involvement
  • Cancer chemotherapy within 2 weeks prior to start of blinatumomab (except for tyrosine kinase inhibitors (TKI) and/or low dose maintenance therapy such as vinca alkaloids, mercaptopurine, methotrexate, glucocorticoids; intrathecal chemotherapy and dexamethasone are allowed until start of blinatumomab).
  • Chemotherapy related toxicities that haven’t resolved to grade 2
  • Radiotherapy within 2 weeks prior to blinatumomab treatment
  • Immunotherapy (eg, rituximab) within 4 weeks prior to blinatumomab 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.
  • Subject has known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing
  • 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 human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive)
  • Subject is pregnant or breast feeding, or is planning to become pregnant within 3 months after the last dose of protocol-specified therapy
  • Adolescent female of childbearing potential and is not willing to use 2 highly effective forms of contraception while receiving blinatumomab and for an additional 3 months after the last dose of protocol-specified therapy
  • Male who has a female partner of childbearing potential and is not willing to use 2 highly effective forms of contraception while receiving blinatumomab and for an additional 3 months after the last dose of protocol-specified therapy
  • Male who has a pregnant partner, and is not willing to use a condom during sexual activity for 3 months after the last dose of protocol-specified therapy
  • Abnormal screening laboratory values as defined below:

Creatinine clearance < 70 mL/min/1.73 m2 OR an abnormal normal serum creatinine based on age/gender prior to day 1

Total bilirubin > 1.5 x upper limit of normal (ULN) for age OR direct bilirubin > 1.5 mg/DL prior to day 1

  • 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.
  • Subjects with Philadelphia chromosome negative (Ph-) high-risk (HR) first relapse B-precursor ALL in continuous CR after treatment, but with molecular failure or molecular relapse defined by MRD level of at least 10^-3.