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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02112916




Registration number
NCT02112916
Ethics application status
Date submitted
9/04/2014
Date registered
14/04/2014
Date last updated
9/08/2024

Titles & IDs
Public title
Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma
Scientific title
A Phase III Randomized Trial Investigating Bortezomib (NSC# 681239) on a Modified Augmented BFM (ABFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LLy)
Secondary ID [1] 0 0
NCI-2014-00712
Secondary ID [2] 0 0
NCI-2014-00712
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adult T Acute Lymphoblastic Leukemia 0 0
Ann Arbor Stage II Adult Lymphoblastic Lymphoma 0 0
Ann Arbor Stage II Childhood Lymphoblastic Lymphoma 0 0
Ann Arbor Stage III Adult Lymphoblastic Lymphoma 0 0
Ann Arbor Stage III Childhood Lymphoblastic Lymphoma 0 0
Ann Arbor Stage IV Adult Lymphoblastic Lymphoma 0 0
Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma 0 0
Childhood T Acute Lymphoblastic Leukemia 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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bortezomib
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Etoposide
Treatment: Drugs - Hydrocortisone Sodium Succinate
Treatment: Drugs - Ifosfamide
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Pegaspargase
Treatment: Other - Radiation Therapy
Treatment: Drugs - Thioguanine
Treatment: Drugs - Vincristine
Treatment: Drugs - Vincristine Sulfate

Active comparator: Arm A (combination chemotherapy) - Patients receive combination chemotherapy without bortezomib. See Detailed Description.

Experimental: Arm B (combination chemotherapy, bortezomib) - Patients receive combination chemotherapy with bortezomib (4 doses at 1.3 mg/m\^2 during Induction and 4 doses at 1.3 mg/m\^2 during Delayed Intensification). See Detailed Description.


Treatment: Drugs: Bortezomib
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Cytarabine
Given IT, IV, or SC

Treatment: Drugs: Daunorubicin
Given IV

Treatment: Drugs: Daunorubicin Hydrochloride
Given IV

Treatment: Drugs: Dexamethasone
Given PO or IV

Treatment: Drugs: Doxorubicin
Given IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Drugs: Hydrocortisone Sodium Succinate
Given IT

Treatment: Drugs: Ifosfamide
Given IV

Treatment: Drugs: Leucovorin Calcium
Given PO or IV

Treatment: Drugs: Mercaptopurine
Give PO

Treatment: Drugs: Methotrexate
Given IT, IV, or PO

Treatment: Drugs: Pegaspargase
Given IV

Treatment: Other: Radiation Therapy
Undergo radiation therapy

Treatment: Drugs: Thioguanine
Given PO

Treatment: Drugs: Vincristine
Given IV

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
Event-free Survival (EFS) for Modified Augmented Berlin-Frankfurt-Munster Backbone With or Without Bortezomib in All Randomized Patients
Timepoint [1] 0 0
3 years
Secondary outcome [1] 0 0
Toxicity Rates Associated With Modified Standard Therapy, Including Dexamethasone and Additional Pegaspargase
Timepoint [1] 0 0
3 years from start of therapy by patient
Secondary outcome [2] 0 0
EFS for Standard (SR) and Intermediate Risk (IR) T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no Cranial Radiation Therapy [CRT]) and Similar Patients on AALL0434 (Received CRT)
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Cumulative Incidence Rates of Isolated Central Nervous System (CNS) Relapse for SR and IR T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no CRT) and Similar Patients on AALL0434 (Receive CRT)
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
EFS for Very High Risk (VHR) T-ALL Patients Treated With High Risk (HR) Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Become Minimal Residual Disease (MRD) Negative and Those Who Remain MRD Positive at the End of HR Block 3
Timepoint [4] 0 0
3 years
Secondary outcome [5] 0 0
EFS for Very High Risk (VHR) T-LLy Patients Treated With HR Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Have Complete or Partial Remission and Those Who do Not Respond
Timepoint [5] 0 0
3 years

Eligibility
Key inclusion criteria
* T-ALL: T-ALL patients must be enrolled on AALL08B1 or Project:EveryChild (APEC14B1, if open for the classification of ALL patients) prior to treatment and enrollment on AALL1231
* All patients must be > 1 and < 31 years of age
* Patients must have newly diagnosed T-lymphoblastic leukemia (T-ALL) or T-lymphoblastic lymphoma (T-LLy) stages II-IV

* Note: a diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (cluster of differentiation [CD]19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a, and are present either in peripheral blood or > 25% in the bone marrow; if surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including terminal deoxynucleotidyl transferase (TdT), CD34 or CD99 will be assessed for expression; cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory
* For T-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-LLy defined by the submitting institution will be accepted
* All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Minimum age
1 Year
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of T-ALL, T-L-Ly or for any cancer diagnosis prior to the initiation of protocol therapy on AALL1231, with the exception of:

* Steroid pretreatment: prednisone or methylprednisolone for =< 120 hours (5 days) in the 7 days prior to initiating induction chemotherapy or for =< 336 hours (14 days) in the 28 days prior to initiating induction chemotherapy; prior exposure to ANY steroids that occurred > 28 days before the initiation of protocol therapy does not affect eligibility; the dose of prednisone or methylprednisolone does not affect eligibility
* Intrathecal cytarabine (the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment) system chemotherapy must begin with 72 hours of this IT therapy; or
* Pretreatment with hydroxyurea; or
* 600 cGy of chest irradiation, if medically necessary

* Pre-treatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone use during sedation to prevent or treat airway edema; inhalation steroids and topical steroids are not considered pretreatment
* Pre-existing >= grade 2 sensory or motor peripheral neurotoxicity
* Uncontrolled seizure disorder
* Diagnosis of Down syndrome (Trisomy 21)
* 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
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* Patient has hypersensitivity to bortezomib, boron, or mannitol
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study
* Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and within 30 days of any dose of bortezomib

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
Princess Margaret Hospital for Children - Perth
Recruitment hospital [8] 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
6008 - Perth
Recruitment postcode(s) [8] 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
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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
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Illinois
Country [15] 0 0
United States of America
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Indiana
Country [16] 0 0
United States of America
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Iowa
Country [17] 0 0
United States of America
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Kentucky
Country [18] 0 0
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Hampshire
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New Jersey
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New Mexico
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Vermont
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Virginia
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Washington
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West Virginia
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Wisconsin
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Alberta
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British Columbia
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Manitoba
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Newfoundland and Labrador
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Nova Scotia
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Ontario
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Saskatchewan
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Auckland
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New Zealand
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Christchurch

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
David T Teachey
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.