Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT02101853
Registration number
NCT02101853
Ethics application status
Date submitted
28/03/2014
Date registered
2/04/2014
Date last updated
24/07/2024
Titles & IDs
Public title
Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia
Query!
Scientific title
Risk-Stratified Randomized Phase III Testing of Blinatumomab (NSC#765986) in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)
Query!
Secondary ID [1]
0
0
NCI-2014-00631
Query!
Secondary ID [2]
0
0
NCI-2014-00631
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Recurrent B Acute Lymphoblastic Leukemia
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Leukaemia - Acute leukaemia
Query!
Cancer
0
0
0
0
Query!
Leukaemia - Chronic leukaemia
Query!
Cancer
0
0
0
0
Query!
Children's - Leukaemia & Lymphoma
Query!
Cancer
0
0
0
0
Query!
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Query!
Cancer
0
0
0
0
Query!
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Surgery - Allogeneic Hematopoietic Stem Cell Transplantation
Treatment: Drugs - Asparaginase
Treatment: Other - Blinatumomab
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Etoposide
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Mitoxantrone
Treatment: Drugs - Mitoxantrone Hydrochloride
Treatment: Drugs - Pegaspargase
Other interventions - Pharmacological Study
Treatment: Other - Radiation Therapy
Treatment: Drugs - Therapeutic Hydrocortisone
Treatment: Drugs - Thioguanine
Treatment: Drugs - Vincristine
Treatment: Drugs - Vincristine Sulfate
Active comparator: Arm A (HR and IR control) - Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT. Closed effective September 18, 2019.
Experimental: Arm B (HR and IR blinatumomab) - Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT.
Active comparator: Arm C (LR control) - Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance.
Experimental: Arm D (LR blinatumomab) - Patients receive Block 2 over 4 weeks, Blinatumomab Cycle 1 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Cycle 2 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Cycle 3 over 5 weeks, and then Maintenance.
Treatment: Surgery: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Treatment: Drugs: Asparaginase
Given IM or IV
Treatment: Other: Blinatumomab
Given IV
Treatment: Drugs: Cyclophosphamide
Given IV
Treatment: Drugs: Cytarabine
Given IT and IV or SC
Treatment: Drugs: Dexamethasone
Given PO or IV
Treatment: Drugs: Etoposide
Given IV
Treatment: Drugs: Leucovorin Calcium
Given IV or PO
Treatment: Drugs: Mercaptopurine
Given PO
Treatment: Drugs: Methotrexate
Given IT, IV, and PO
Treatment: Drugs: Mitoxantrone
Given IV
Treatment: Drugs: Mitoxantrone Hydrochloride
Given IV
Treatment: Drugs: Pegaspargase
Given IV
Other interventions: Pharmacological Study
Correlative studies
Treatment: Other: Radiation Therapy
Undergo cranial radiation therapy
Treatment: Drugs: Therapeutic Hydrocortisone
Given IT
Treatment: Drugs: Thioguanine
Given PO
Treatment: Drugs: Vincristine
Given IV
Treatment: Drugs: Vincristine Sulfate
Given IV
Query!
Intervention code [1]
0
0
Treatment: Surgery
Query!
Intervention code [2]
0
0
Treatment: Drugs
Query!
Intervention code [3]
0
0
Treatment: Other
Query!
Intervention code [4]
0
0
Other interventions
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Disease Free Survival (DFS) of High-risk (HR) and Intermediate-risk (IR) Relapse Patients
Query!
Assessment method [1]
0
0
DFS rates of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization). DFS is calculated as the time from randomization to date of first event (treatment failure, relapse, second malignancy, remission death) or date of last contact. Two-year DFS estimates will be calculated from date of randomization for both Arm A and Arm B. Two-sided 95% confidence intervals will be calculated.
Query!
Timepoint [1]
0
0
Up to 2 years from date of randomization
Query!
Primary outcome [2]
0
0
Disease Free Survival (DFS) of Low Risk (LR) Relapse Patients
Query!
Assessment method [2]
0
0
DFS rates of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization). DFS is calculated as the time from randomization to date of first event (relapse, second malignancy, remission death) or date of last contact. Three-year DFS estimates will be calculated from date of randomization for both Arm C and Arm D. Two-sided 95% confidence intervals will be calculated.
Query!
Timepoint [2]
0
0
Up to 3 years from date of randomization
Query!
Secondary outcome [1]
0
0
Overall Survival (OS) of HR and IR Relapse Patients
Query!
Assessment method [1]
0
0
OS rates of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization). OS is calculated as the time from randomization to date of death or date of last contact. Two-year OS estimates will be calculated from date of randomization for both Arm A and Arm B. Two-sided 95% confidence intervals will be calculated.
Query!
Timepoint [1]
0
0
Up to 2 years from date of randomization
Query!
Secondary outcome [2]
0
0
Overall Survival (OS) of LR Relapse Patients
Query!
Assessment method [2]
0
0
OS rates of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization). OS is calculated as the time from randomization to date of death or date of last contact. Three-year OS estimates will be calculated from date of randomization for both Arm C and Arm D. Two-sided 95% confidence intervals will be calculated.
Query!
Timepoint [2]
0
0
Up to 3 years from date of randomization
Query!
Eligibility
Key inclusion criteria
* Patients >= 1 year and < 31 years of age at the time of relapse will be eligible
* First relapse of B-ALL, allowable sites of disease include isolated bone marrow, combined bone marrow and CNS and/or testicular, and isolated CNS and/or testicular; extramedullary sites are limited to the CNS and testicles
* No waiting period for patients who relapse while receiving standard maintenance therapy
* Patients who relapse on frontline therapy in phases other than maintenance must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
* Cytotoxic therapy: at least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy, or maintenance chemotherapy, or intrathecal chemotherapy (methotrexate strongly preferred) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status
* Biologic (anti-neoplastic) agent: at least 7 days since the completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Stem cell transplant or rescue: patient has not had a prior stem cell transplant or rescue
* Patient has not had prior treatment with blinatumomab
* With the exception of intrathecal chemotherapy (methotrexate strongly preferred; cytarabine is permissible) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status, patient has not received prior relapse-directed therapy (i.e., this protocol is intended as the INITIAL treatment of first relapse)
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
* 1 to < 2 years: =< 0.6 mg/dL
* 2 to < 6 years: =< 0.8 mg/dL
* 6 to < 10 years: =< 1 mg/dL
* 10 to < 13 years: =< 1.2 mg/dL
* 13 to < 16 years: =< 1.5 mg/dL (males) and =< 1.4 mg/dL (females)
* >= 16 years: =< 1.7 mg/dL (males) and =< 1.4 mg/dL (females)
* Direct bilirubin < 3.0 mg/dL
* Shortening fraction of >= 27% by echocardiogram, or
* Ejection fraction of >= 50% by radionuclide angiogram
* All patients and/or their parent or legal guardian must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Query!
Minimum age
1
Year
Query!
Query!
Maximum age
31
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* Patients with Philadelphia chromosome positive/breakpoint cluster region protein (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)+ ALL are not eligible
* Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia are not eligible
* Patients with T-lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (T-LL) are not eligible
* Patients with B-lymphoblastic lymphoma (B-LL) are not eligible
* Patients with known optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
* Patients known to have one of the following concomitant genetic syndromes: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
* Patients with known human immunodeficiency virus (HIV) infection
* Patients with known allergy to mitoxantrone, cytarabine, or both etoposide and etoposide phosphate (Etopophos)
* Lactating females who plan to breastfeed
* Patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* Patients with pre-existing significant central nervous system pathology that would preclude treatment with blinatumomab, including: history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder, or autoimmune disease with CNS involvement are not eligible; patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible; (patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved)
* Patients with uncontrolled seizure disorder are not eligible; (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs remain eligible)
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Active, not recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
17/12/2014
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
22/09/2024
Query!
Actual
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
669
Query!
Recruitment in Australia
Recruitment state(s)
WA
Query!
Recruitment hospital [1]
0
0
Princess Margaret Hospital for Children - Perth
Query!
Recruitment hospital [2]
0
0
Perth Children's Hospital - Perth
Query!
Recruitment postcode(s) [1]
0
0
6008 - Perth
Query!
Recruitment postcode(s) [2]
0
0
6009 - Perth
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Alabama
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Alaska
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Arizona
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Arkansas
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
California
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Colorado
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Connecticut
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Delaware
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
District of Columbia
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Florida
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Georgia
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
Hawaii
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Idaho
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Illinois
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
Indiana
Query!
Country [16]
0
0
United States of America
Query!
State/province [16]
0
0
Kentucky
Query!
Country [17]
0
0
United States of America
Query!
State/province [17]
0
0
Louisiana
Query!
Country [18]
0
0
United States of America
Query!
State/province [18]
0
0
Maine
Query!
Country [19]
0
0
United States of America
Query!
State/province [19]
0
0
Maryland
Query!
Country [20]
0
0
United States of America
Query!
State/province [20]
0
0
Massachusetts
Query!
Country [21]
0
0
United States of America
Query!
State/province [21]
0
0
Michigan
Query!
Country [22]
0
0
United States of America
Query!
State/province [22]
0
0
Minnesota
Query!
Country [23]
0
0
United States of America
Query!
State/province [23]
0
0
Mississippi
Query!
Country [24]
0
0
United States of America
Query!
State/province [24]
0
0
Missouri
Query!
Country [25]
0
0
United States of America
Query!
State/province [25]
0
0
Nebraska
Query!
Country [26]
0
0
United States of America
Query!
State/province [26]
0
0
Nevada
Query!
Country [27]
0
0
United States of America
Query!
State/province [27]
0
0
New Hampshire
Query!
Country [28]
0
0
United States of America
Query!
State/province [28]
0
0
New Jersey
Query!
Country [29]
0
0
United States of America
Query!
State/province [29]
0
0
New York
Query!
Country [30]
0
0
United States of America
Query!
State/province [30]
0
0
North Carolina
Query!
Country [31]
0
0
United States of America
Query!
State/province [31]
0
0
Ohio
Query!
Country [32]
0
0
United States of America
Query!
State/province [32]
0
0
Oklahoma
Query!
Country [33]
0
0
United States of America
Query!
State/province [33]
0
0
Oregon
Query!
Country [34]
0
0
United States of America
Query!
State/province [34]
0
0
Pennsylvania
Query!
Country [35]
0
0
United States of America
Query!
State/province [35]
0
0
Rhode Island
Query!
Country [36]
0
0
United States of America
Query!
State/province [36]
0
0
South Carolina
Query!
Country [37]
0
0
United States of America
Query!
State/province [37]
0
0
South Dakota
Query!
Country [38]
0
0
United States of America
Query!
State/province [38]
0
0
Tennessee
Query!
Country [39]
0
0
United States of America
Query!
State/province [39]
0
0
Texas
Query!
Country [40]
0
0
United States of America
Query!
State/province [40]
0
0
Utah
Query!
Country [41]
0
0
United States of America
Query!
State/province [41]
0
0
Virginia
Query!
Country [42]
0
0
United States of America
Query!
State/province [42]
0
0
Washington
Query!
Country [43]
0
0
United States of America
Query!
State/province [43]
0
0
West Virginia
Query!
Country [44]
0
0
United States of America
Query!
State/province [44]
0
0
Wisconsin
Query!
Country [45]
0
0
Canada
Query!
State/province [45]
0
0
British Columbia
Query!
Country [46]
0
0
Canada
Query!
State/province [46]
0
0
Manitoba
Query!
Country [47]
0
0
Canada
Query!
State/province [47]
0
0
Newfoundland and Labrador
Query!
Country [48]
0
0
Canada
Query!
State/province [48]
0
0
Nova Scotia
Query!
Country [49]
0
0
Canada
Query!
State/province [49]
0
0
Ontario
Query!
Country [50]
0
0
Canada
Query!
State/province [50]
0
0
Quebec
Query!
Country [51]
0
0
Canada
Query!
State/province [51]
0
0
Saskatchewan
Query!
Country [52]
0
0
New Zealand
Query!
State/province [52]
0
0
Auckland
Query!
Country [53]
0
0
New Zealand
Query!
State/province [53]
0
0
Christchurch
Query!
Country [54]
0
0
Puerto Rico
Query!
State/province [54]
0
0
Caguas
Query!
Country [55]
0
0
Puerto Rico
Query!
State/province [55]
0
0
San Juan
Query!
Funding & Sponsors
Primary sponsor type
Government body
Query!
Name
National Cancer Institute (NCI)
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Immunotherapy with blinatumomab may allow the body's immune system to attack and destroy some types of leukemia cells. It is not yet known whether blinatumomab is more effective than standard combination chemotherapy in treating relapsed B-cell acute lymphoblastic leukemia.
Query!
Trial website
https://clinicaltrials.gov/study/NCT02101853
Query!
Trial related presentations / publications
Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, Raetz EA, Zugmaier G, Sharon E, Bernhardt MB, Terezakis SA, Gore L, Whitlock JA, Pulsipher MA, Hunger SP, Loh ML. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):833-842. doi: 10.1001/jama.2021.0669.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Patrick A Brown
Query!
Address
0
0
Children's Oncology Group
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
Study Protocol and Statistical Analysis Plan
https://cdn.clinicaltrials.gov/large-docs/53/NCT02101853/Prot_SAP_000.pdf
Statistical analysis plan
Study Protocol and Statistical Analysis Plan
https://cdn.clinicaltrials.gov/large-docs/53/NCT02101853/Prot_SAP_000.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT02101853
Download to PDF