Please note that the ANZCTR will be unattended from Friday the 17th of July to Monday the 20th of July 2020 inclusive. Thank you and apologies for any inconvenience caused.

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
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02101853




Registration number
NCT02101853
Ethics application status
Date submitted
28/03/2014
Date registered
2/04/2014
Date last updated
18/06/2020

Titles & IDs
Public title
Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia
Scientific title
Risk-Stratified Randomized Phase III Testing of Blinatumomab (NSC#765986) in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)
Secondary ID [1] 0 0
NCI-2014-00631
Secondary ID [2] 0 0
NCI-2014-00631
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent B Acute Lymphoblastic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Allogeneic Hematopoietic Stem Cell Transplantation
Treatment: Drugs - Asparaginase
Other interventions - Blinatumomab
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Etoposide
Other interventions - Laboratory Biomarker Analysis
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

Other interventions: 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

Other interventions: Laboratory Biomarker Analysis
Correlative studies

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

Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Intervention code [4] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapse patients - Comparison of DFS rates between treatment arms will be based on log rank test. Interim analysis will be conducted to monitor for efficacy and futility. The efficacy stopping boundaries are based on the O' Brien-Fleming spending function. The futility boundaries are based on testing the alternative hypothesis at the 0.024 level.
Timepoint [1] 0 0
From randomization to first event (treatment failure, relapse, second malignancy, death) or last follow-up for those who are event-free, assessed up to 10 years
Primary outcome [2] 0 0
DFS of low risk (LR) relapse patients - Comparison of DFS rates between treatment arms will be based on log rank test. Interim analysis will be conducted to monitor for efficacy and futility. The efficacy stopping boundaries are based on the O' Brien-Fleming spending function. The futility boundaries are based on testing the alternative hypothesis at the 0.039 level.
Timepoint [2] 0 0
From randomization to first event (relapse, second malignancy, death) or last follow-up for those who are event-free, assessed up to 10 years
Secondary outcome [1] 0 0
Overall survival (OS) of HR and IR relapse patients - Comparison of OS rates between treatment arms will be based on log rank test.
Timepoint [1] 0 0
From randomization to death or last follow-up, assessed up to 10 years
Secondary outcome [2] 0 0
OS of lLR relapse patients - Comparison of OS rates between treatment arms will be based on log rank test.
Timepoint [2] 0 0
From randomization to death or last follow-up, assessed up to 10 years

Eligibility
Key inclusion criteria
- 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
Minimum age
1 Year
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [2] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
6008 - Perth
Recruitment postcode(s) [2] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
Arkansas
Country [5] 0 0
United States of America
State/province [5] 0 0
California
Country [6] 0 0
United States of America
State/province [6] 0 0
Colorado
Country [7] 0 0
United States of America
State/province [7] 0 0
Connecticut
Country [8] 0 0
United States of America
State/province [8] 0 0
Delaware
Country [9] 0 0
United States of America
State/province [9] 0 0
District of Columbia
Country [10] 0 0
United States of America
State/province [10] 0 0
Florida
Country [11] 0 0
United States of America
State/province [11] 0 0
Georgia
Country [12] 0 0
United States of America
State/province [12] 0 0
Hawaii
Country [13] 0 0
United States of America
State/province [13] 0 0
Idaho
Country [14] 0 0
United States of America
State/province [14] 0 0
Illinois
Country [15] 0 0
United States of America
State/province [15] 0 0
Indiana
Country [16] 0 0
United States of America
State/province [16] 0 0
Kentucky
Country [17] 0 0
United States of America
State/province [17] 0 0
Louisiana
Country [18] 0 0
United States of America
State/province [18] 0 0
Maine
Country [19] 0 0
United States of America
State/province [19] 0 0
Maryland
Country [20] 0 0
United States of America
State/province [20] 0 0
Massachusetts
Country [21] 0 0
United States of America
State/province [21] 0 0
Michigan
Country [22] 0 0
United States of America
State/province [22] 0 0
Minnesota
Country [23] 0 0
United States of America
State/province [23] 0 0
Mississippi
Country [24] 0 0
United States of America
State/province [24] 0 0
Missouri
Country [25] 0 0
United States of America
State/province [25] 0 0
Nebraska
Country [26] 0 0
United States of America
State/province [26] 0 0
Nevada
Country [27] 0 0
United States of America
State/province [27] 0 0
New Hampshire
Country [28] 0 0
United States of America
State/province [28] 0 0
New Jersey
Country [29] 0 0
United States of America
State/province [29] 0 0
New York
Country [30] 0 0
United States of America
State/province [30] 0 0
North Carolina
Country [31] 0 0
United States of America
State/province [31] 0 0
Ohio
Country [32] 0 0
United States of America
State/province [32] 0 0
Oklahoma
Country [33] 0 0
United States of America
State/province [33] 0 0
Oregon
Country [34] 0 0
United States of America
State/province [34] 0 0
Pennsylvania
Country [35] 0 0
United States of America
State/province [35] 0 0
Rhode Island
Country [36] 0 0
United States of America
State/province [36] 0 0
South Carolina
Country [37] 0 0
United States of America
State/province [37] 0 0
South Dakota
Country [38] 0 0
United States of America
State/province [38] 0 0
Tennessee
Country [39] 0 0
United States of America
State/province [39] 0 0
Texas
Country [40] 0 0
United States of America
State/province [40] 0 0
Utah
Country [41] 0 0
United States of America
State/province [41] 0 0
Virginia
Country [42] 0 0
United States of America
State/province [42] 0 0
Washington
Country [43] 0 0
United States of America
State/province [43] 0 0
West Virginia
Country [44] 0 0
United States of America
State/province [44] 0 0
Wisconsin
Country [45] 0 0
Canada
State/province [45] 0 0
British Columbia
Country [46] 0 0
Canada
State/province [46] 0 0
Manitoba
Country [47] 0 0
Canada
State/province [47] 0 0
Newfoundland and Labrador
Country [48] 0 0
Canada
State/province [48] 0 0
Nova Scotia
Country [49] 0 0
Canada
State/province [49] 0 0
Ontario
Country [50] 0 0
Canada
State/province [50] 0 0
Quebec
Country [51] 0 0
Canada
State/province [51] 0 0
Saskatchewan
Country [52] 0 0
New Zealand
State/province [52] 0 0
Auckland
Country [53] 0 0
New Zealand
State/province [53] 0 0
Christchurch
Country [54] 0 0
Puerto Rico
State/province [54] 0 0
Caguas
Country [55] 0 0
Puerto Rico
State/province [55] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

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
induce changes in body's immune system and may interfere with the ability of tumor cells to
grow and spread. It is not yet known whether standard combination chemotherapy is more
effective than blinatumomab in treating relapsed B-cell acute lymphoblastic leukemia.
Trial website
https://clinicaltrials.gov/show/NCT02101853
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Patrick A Brown
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications