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/NCT02339740




Registration number
NCT02339740
Ethics application status
Date submitted
13/01/2015
Date registered
15/01/2015
Date last updated
10/03/2020

Titles & IDs
Public title
Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia
Scientific title
A Phase III Study for Patients With Newly Diagnosed Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide and All-Trans Retinoic Acid
Secondary ID [1] 0 0
NCI-2014-02266
Secondary ID [2] 0 0
AAML1331
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Promyelocytic Leukemia With PML-RARA 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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Arsenic Trioxide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Idarubicin
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Mitoxantrone Hydrochloride
Other interventions - Quality-of-Life Assessment
Other interventions - Questionnaire Administration
Treatment: Drugs - Tretinoin

Experimental: Treatment (tretinoin, arsenic trioxide, chemotherapy) - See Detailed Description


Treatment: Drugs: Arsenic Trioxide
Given IV

Treatment: Drugs: Cytarabine
Given IV

Treatment: Drugs: Dexamethasone
Given PO or IV

Treatment: Drugs: Idarubicin
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Mitoxantrone Hydrochloride
Given IV

Other interventions: Quality-of-Life Assessment
Ancillary studies

Other interventions: Questionnaire Administration
Ancillary studies

Treatment: Drugs: Tretinoin
Given PO

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

Outcomes
Primary outcome [1] 0 0
Event-free survival (EFS) in standard risk acute promyelocytic leukemia (APL) patients - EFS is defined as the time from on study to failure to achieve hematological complete response (CR) prior to start of consolidation, persistence of molecular positive disease after minimal residual disease (MRD) positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. The Kaplan-Meier method will be used to estimate 2-year EFS along with 90% log-minus-log transformed confidence limits.
Timepoint [1] 0 0
Up to 24 months
Primary outcome [2] 0 0
EFS in high risk APL patients - EFS is defined as the time from on study to failure to achieve hematological CR prior to start of consolidation, persistence of molecular positive disease after MRD positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. The Kaplan-Meier method will be used to estimate 2-year EFS along with 90% log-minus-log transformed confidence limits.
Timepoint [2] 0 0
Up to 24 months

Eligibility
Key inclusion criteria
- Patients must be newly diagnosed with a clinical diagnosis of APL (initially by
morphology of bone marrow or peripheral blood)

- Bone marrow is highly preferred but in cases where marrow cannot be obtained at
diagnosis, peripheral blood will be accepted

- If the RQ-PCR results are known at the time of study enrollment, the patient must
demonstrate the PML-RARalpha transcript by RQ-PCR to be eligible

- NOTE: A lumbar puncture is not required in order to be enrolled on study nor are
lumbar punctures recommended at the time of diagnosis; if the diagnosis of APL is
known or suspected, diagnostic lumbar punctures in patients with neurologic symptoms
should be deferred until any coagulopathy is corrected; if central nervous system
(CNS) disease is suspected or proven, a computed tomography (CT) or magnetic resonance
imaging (MRI) should be considered to rule out the possibility of an associated
chloroma; if CNS disease is documented, patients are still eligible and will receive
protocol directed intrathecal treatments

- Patients may receive up to a maximum of 5 days of pre-treatment with ATRA prior to
administration of protocol therapy

- Treatment with hydroxyurea, corticosteroids (any route) and intrathecal cytarabine
prior to beginning protocol directed therapy is allowed; however, it should be noted
that lumbar puncture and intrathecal therapy at initial diagnosis of APL is not
recommended

- 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
12 Months
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with secondary APL are excluded; this includes all patients with APL that may
have resulted from prior treatment (chemotherapy or radiation)

- Patients with isolated myeloid sarcoma (myeloblastoma, chloroma, including leukemia
cutis) but without evidence of APL by bone marrow or peripheral blood morphology are
excluded

- Patients with a pre-existing diagnosis of a prolonged QT syndrome (even if corrected
QT interval [QTc] is normal at the time of APL diagnosis) are excluded

- Patients with a baseline QTc of > 450 msec are excluded; Bazett?s formula is to be
used for measurement of the corrected QT interval: the QT interval (msec) divided by
the square root of the RR interval (msec)

- Patients with a history or presence of significant ventricular or atrial
tachyarrhythmia are excluded

- Patients with right bundle branch block plus left anterior hemiblock, bifascicular
block are excluded

- Patients with serum creatinine > 3.0 mg/dL and patients on active dialysis for renal
dysfunction are excluded

- Patients who have received treatment with any other cytotoxic chemotherapy prior to
beginning protocol therapy (other than allowed in above criteria) are excluded

- Female patients who are pregnant are excluded; patients should not be pregnant or plan
to become pregnant while on treatment; a pregnancy test prior to enrollment is
required for female patients of childbearing potential

- Lactating females who plan to breastfeed their infants are excluded

- Sexually active patients of reproductive potential who have not agreed to be abstinent
or use 2 forms of effective contraception during treatment through 1 month off therapy
are excluded

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Single group
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
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [5] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
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
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5006 - North Adelaide
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
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
Iowa
Country [17] 0 0
United States of America
State/province [17] 0 0
Kentucky
Country [18] 0 0
United States of America
State/province [18] 0 0
Louisiana
Country [19] 0 0
United States of America
State/province [19] 0 0
Maine
Country [20] 0 0
United States of America
State/province [20] 0 0
Maryland
Country [21] 0 0
United States of America
State/province [21] 0 0
Massachusetts
Country [22] 0 0
United States of America
State/province [22] 0 0
Michigan
Country [23] 0 0
United States of America
State/province [23] 0 0
Minnesota
Country [24] 0 0
United States of America
State/province [24] 0 0
Mississippi
Country [25] 0 0
United States of America
State/province [25] 0 0
Missouri
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
North Dakota
Country [32] 0 0
United States of America
State/province [32] 0 0
Ohio
Country [33] 0 0
United States of America
State/province [33] 0 0
Oklahoma
Country [34] 0 0
United States of America
State/province [34] 0 0
Oregon
Country [35] 0 0
United States of America
State/province [35] 0 0
Pennsylvania
Country [36] 0 0
United States of America
State/province [36] 0 0
Rhode Island
Country [37] 0 0
United States of America
State/province [37] 0 0
South Carolina
Country [38] 0 0
United States of America
State/province [38] 0 0
South Dakota
Country [39] 0 0
United States of America
State/province [39] 0 0
Tennessee
Country [40] 0 0
United States of America
State/province [40] 0 0
Texas
Country [41] 0 0
United States of America
State/province [41] 0 0
Utah
Country [42] 0 0
United States of America
State/province [42] 0 0
Virginia
Country [43] 0 0
United States of America
State/province [43] 0 0
Washington
Country [44] 0 0
United States of America
State/province [44] 0 0
West Virginia
Country [45] 0 0
United States of America
State/province [45] 0 0
Wisconsin
Country [46] 0 0
Canada
State/province [46] 0 0
Manitoba
Country [47] 0 0
Canada
State/province [47] 0 0
Nova Scotia
Country [48] 0 0
Canada
State/province [48] 0 0
Ontario
Country [49] 0 0
Canada
State/province [49] 0 0
Quebec
Country [50] 0 0
New Zealand
State/province [50] 0 0
Auckland
Country [51] 0 0
New Zealand
State/province [51] 0 0
Christchurch
Country [52] 0 0
Puerto Rico
State/province [52] 0 0
Caguas
Country [53] 0 0
Puerto Rico
State/province [53] 0 0
San Juan
Country [54] 0 0
Saudi Arabia
State/province [54] 0 0
Riyadh

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This phase III trial studies tretinoin and arsenic trioxide in treating patients with newly
diagnosed acute promyelocytic leukemia. Standard treatment for acute promyelocytic leukemia
involves high doses of a common class of chemotherapy drugs called anthracyclines, which are
known to cause long-term side effects, especially to the heart. Tretinoin may stop the growth
of cancer cells by blocking some of the enzymes needed for cell growth. Arsenic trioxide may
stop the growth of cancer cells by either killing the cells, by stopping them from dividing,
or by stopping them from spreading. Completely removing or reducing the amount of
anthracycline chemotherapy and giving tretinoin together with arsenic trioxide may be an
effective treatment for acute promyelocytic leukemia and may reduce some of the long-term
side effects.
Trial website
https://clinicaltrials.gov/show/NCT02339740
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Matthew A Kutny
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