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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03914625




Registration number
NCT03914625
Ethics application status
Date submitted
12/04/2019
Date registered
16/04/2019

Titles & IDs
Public title
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
Scientific title
A Phase 3 Trial Investigating Blinatumomab (NSC# 765986) in Combination With Chemotherapy in Patients With Newly Diagnosed Standard Risk or Down Syndrome B-Lymphoblastic Leukemia (B-ALL) and the Treatment of Patients With Localized B-Lymphoblastic Lymphoma (B-LLy)
Secondary ID [1] 0 0
NCI-2019-02187
Secondary ID [2] 0 0
NCI-2019-02187
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B Acute Lymphoblastic Leukemia 0 0
B Lymphoblastic Lymphoma 0 0
Down Syndrome 0 0
Condition category
Condition code
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
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
Human Genetics and Inherited Disorders 0 0 0 0
Down's syndrome
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Asparaginase Erwinia chrysanthemi
Treatment: Other - Blinatumomab
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Mercaptopurine Oral Suspension
Treatment: Drugs - Methotrexate
Treatment: Drugs - Pegaspargase
Treatment: Drugs - Prednisolone
Treatment: Drugs - Prednisone
Treatment: Other - Radiation Therapy
Treatment: Other - Radiation Therapy
Treatment: Drugs - Thioguanine
Treatment: Drugs - Vincristine Sulfate

Active comparator: Arm A (SR-Avg control) - Arm A: See detailed description.

Experimental: Arm B (SR-Avg experimental) - Arm B: See detailed description.

Active comparator: Arm C (SR-High Control) - Arm C: See detailed description.

Experimental: Arm D (SR-High experimental) - Arm D See detailed description.

Experimental: B-LLy - See detailed description.

Experimental: DS B-ALL - See detailed description.

Experimental: NCI SR or HR DS B-ALL - See detailed description.


Treatment: Drugs: Asparaginase Erwinia chrysanthemi
Given IV or IM

Treatment: Other: Blinatumomab
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Cytarabine
Given IT or IV

Treatment: Drugs: Dexamethasone
Given PO or IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Leucovorin Calcium
Given PO or IV

Treatment: Drugs: Mercaptopurine
Given PO

Treatment: Drugs: Mercaptopurine Oral Suspension
Given PO

Treatment: Drugs: Methotrexate
Given IT or IV

Treatment: Drugs: Pegaspargase
Given IV or IM

Treatment: Drugs: Prednisolone
Given PO or IV

Treatment: Drugs: Prednisone
Given PO or IV

Treatment: Other: Radiation Therapy
Undergo cranial radiation therapy

Treatment: Other: Radiation Therapy
Undergo testicular radiation therapy

Treatment: Drugs: Thioguanine
Given PO

Treatment: Drugs: Vincristine Sulfate
Given IV

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

Outcomes
Primary outcome [1] 0 0
Disease free survival (DFS) in randomization eligible patients with higher risk features (SR-High) or standard risk average (SR-Avg) B-ALL patients based on randomization with addition of blinatumomab
Timepoint [1] 0 0
5.3 years
Primary outcome [2] 0 0
DFS in boys in the SR-favorable subset of SR B-ALL with or without Down syndrome (DS)
Timepoint [2] 0 0
5.1 years
Secondary outcome [1] 0 0
DFS for patients with SR-Avg B-ALL who are negative for MRD measured by flow cytometry and HTS at EOI when treated with standard chemotherapy with a treatment duration of 2 years from the start of interim maintenance (IM)1, regardless of sex
Timepoint [1] 0 0
5.1 years
Secondary outcome [2] 0 0
DFS for patients with standard-risk favorable (SR-Fav) B-ALL when treated with a standard chemotherapy regimen
Timepoint [2] 0 0
5.1 years
Secondary outcome [3] 0 0
Treatment-related mortality in Down syndrome high risk (DS-high) patients after replacement of intensive elements of standard chemotherapy (omission of anthracyclines in induction, omission of the second month of DI) with 3 cycles of blinatumomab
Timepoint [3] 0 0
2.3 years
Secondary outcome [4] 0 0
DFS of DS-High B-ALL patients when intensive elements of chemotherapy are replaced with 3 cycles of blinatumomab
Timepoint [4] 0 0
5.3 years
Secondary outcome [5] 0 0
DFS of patients with localized B-lymphoblastic lymphoma (B-LLy) receiving standard risk acute lymphoblastic leukemia therapy
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
Change in neurocognitive functioning from baseline to end-of-therapy between children from poor (defined as presence of household material hardship [HMH], including either food, housing or energy insecurity) and non-poor families (absence of HMH)
Timepoint [6] 0 0
3.3 years
Secondary outcome [7] 0 0
Caregiver burden as measured by the Mean Total score from the Care of My Child with Cancer questionnaire among a subset of children enrolled in the HMH and neurocognitive outcome study
Timepoint [7] 0 0
1 year
Secondary outcome [8] 0 0
Caregiver burden as measured by the At-Work Productivity Loss summary score from the Caregiver Work Limitations questionnaire among a subset of children enrolled in the HMH and neurocognitive outcome study
Timepoint [8] 0 0
1 year
Secondary outcome [9] 0 0
Peripheral blood (PB) samples using HTS MRD vs. bone marrow (BM) results at EOI
Timepoint [9] 0 0
1 year
Secondary outcome [10] 0 0
BM using HTS MRD vs. BM by flow cytometry at EOC in patients who were Day 29 MRD positive by flow cytometry
Timepoint [10] 0 0
1 year

Eligibility
Key inclusion criteria
* All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement for B-LLy patients. B-LLy patients may directly enroll on AALL1731.
* Age at diagnosis:

* Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).
* Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).
* Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or without DS).
* B-ALL patients without DS must have an initial white blood cell count < 50,000/uL (performed within 7 days prior to enrollment).
* B-ALL patients with DS are eligible regardless of the presenting white blood cell count (WBC) (performed within 7 days prior to enrollment).
* Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on a bone marrow (BM) aspirate;

* OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis can be established by a pathologic diagnosis of B-ALL on a BM biopsy;
* OR a complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells;
* OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without Down syndrome.
* Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted (diagnostic biopsy for B-LLy must be performed within 14 days prior to enrollment).
* All patients and/or their parents or legal guardians 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
365 Days
Maximum age
31 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior history of transient myeloproliferative disease (TMD) are not considered to have had a prior malignancy. They would therefore be eligible whether or not the TMD was treated with cytarabine.
* With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1731.
* For patients receiving steroid pretreatment, the following additional exclusion criteria apply:

* Non-DS B-ALL patients must not have received steroids for more than 24 hours in the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to initiation of the steroids.
* DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV steroids within 4 weeks of diagnosis.
* Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior to the start of systemic protocol therapy.
* B-ALL patients who do not have sufficient diagnostic bone marrow submitted for APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells.
* Patient must not have acute undifferentiated leukemia (AUL).
* Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be known prior to enrollment).

* Note: DS patients with CNS3 disease are eligible but will be assigned to the DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment.
* Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular disease are eligible but will be assigned to the DS-High B-ALL arm).
* For LLy patients, the following additional exclusion criteria apply:

* T-Lymphoblastic Lymphoma.
* Morphologically unclassifiable lymphoma.
* Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
* CNS positive disease or testicular involvement.
* M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow.
* Patients with known Charcot-Marie-Tooth disease.
* Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
* Patients requiring radiation at diagnosis.
* Female 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.
* Lactating females who plan to breastfeed their infants.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.

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)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [4] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [5] 0 0
Monash Medical Center-Clayton Campus - Clayton
Recruitment hospital [6] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [7] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3052 - Parkville
Recruitment postcode(s) [7] 0 0
6009 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Alaska
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Arizona
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Arkansas
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Idaho
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Illinois
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Auckland
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Christchurch
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Caguas
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San Juan

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sumit Gupta
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://grants.nih.gov/policy/sharing.htm


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.