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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02112916
Ethics application status
Date submitted
9/04/2014
Date registered
14/04/2014
Date last updated
12/03/2021

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. 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 - EFS is calculated as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignancy, remission death) or date of last contact. Three-year EFS rates will be calculated for both groups.
Timepoint [1] 0 0
3 years
Secondary outcome [1] 0 0
Incidence of toxicity associated with modified standard therapy, including dexamethasone and additional pegaspargase - Will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Safety data will be provided for the two randomized arms.
Timepoint [1] 0 0
Up to 10 years
Secondary outcome [2] 0 0
EFS for standard (SR) and intermediate risk (IR) patients on the non-bortezomib containing arm on this study (no cranial radiation therapy [CRT]) and similar patients on AALL0434 (received CRT) - Includes T-ALL patients on AALL0434 who received prophylactic cranial radiation and did not receive nelarabine (exclude Low Risk, CNS3, M3 Day 29, and EOC MRD >0.1%); Includes T-ALL patients on AALL1231 who did not receive prophylactic cranial radiation and did not receive bortezomib: Intermediate Risk T-ALL (exclude CNS3) and SR T-ALL (exclude those who met AALL0434 Low Risk definition).Three-year EFS will be calculated for the two groups.
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Cumulative incidence rates of isolated CNS, isolated bone marrow, and combined bone marrow relapse for SR and IR patients on the non-bortezomib containing arm on this study (no CRT) and similar patients on AALL0434 (receive CRT) - Includes T-ALL patients on AALL0434 who received prophylactic cranial radiation and did not receive nelarabine (exclude Low Risk, CNS3, M3 Day 29, and EOC MRD >0.1%); Includes T-ALL patients on AALL1231 who did not receive prophylactic cranial radiation and did not receive bortezomib: Intermediate Risk T-ALL (exclude CNS3) and SR T-ALL (exclude those who met AALL0434 Low Risk definition).Three-year cumulative incidence rates of isolated CNS, isolated bone marrow, and combined bone marrow relapse will be calculated for the two groups.
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 - The proportion of VHR T-ALL patients (with end of consolidation [EOC] MRD >= 0.1%) who become MRD negative (MRD undetectable) after the three high-risk BFM blocks of therapy, will be estimated. EFS will be calculated as time from the end of the three high-risk blocks of therapy to first event (relapse, second malignancy, remission death) or date of last contact. Three-year EFS will be calculated for those patients who are MRD negative at the end of the three high-risk blocks (and continue on chemotherapy) and for those who continue to have detectable MRD at that point (and may receive other treatment options including hematopoietic stem cell transplant).
Timepoint [4] 0 0
3 years
Secondary outcome [5] 0 0
EFS for very high risk (VHR) T-cell lymphoblastic lymphoma patients treated with HR Berlin-Frankfurt-Munster (BFM) intensification blocks who have complete or partial remission and those who do not respond - EFS will be calculated as time from the end of high-risk blocks of therapy to first event (relapse, second malignancy, remission death) or date of last contact. Three-year EFS will be calculated for those patients who have complete or partial response (CR/PR) at the end of the high-risk blocks and for those who don't respond (NR).
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
Gender
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
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Alabama
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Alaska
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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 compares how well combination chemotherapy works when given
with or without bortezomib in treating patients with newly diagnosed T-cell acute
lymphoblastic leukemia or stage II-IV T-cell lymphoblastic lymphoma. Bortezomib may help
reduce the number of leukemia or lymphoma cells by blocking some of the enzymes needed for
cell growth. It may also help chemotherapy work better by making cancer cells more sensitive
to the drugs. It is not yet known if giving standard chemotherapy with or without bortezomib
is more effective in treating newly diagnosed T-cell acute lymphoblastic leukemia and T-cell
lymphoblastic lymphoma.
Trial website
https://clinicaltrials.gov/show/NCT02112916
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

Summary results
Other publications