Acute Promyelocytic Leukemia With t(15;17)(q24.1;q21.2); PML-RARAPhase 3NCT02339740
Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia
A Phase 3 study testing Arsenic Trioxide, Cytarabine and Dexamethasone in people with Acute Promyelocytic Leukemia With t(15;17)(q24.1;q21.2); PML-RARA, run by Children's Oncology Group at 174 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 months to 21 years
- Conditions the study is for
- Acute Promyelocytic Leukemia With t(15;17)(q24.1;q21.2); PML-RARA
- What is being tested?
- Arsenic Trioxide, Cytarabine and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 158 participants
- Where
- 174 sitesin 6 countries
- Study dates
- 21 Jul 2015to 30 Jun 2029
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
174 sites in 6 countries.
174 sites in 6 countries
United States152 sites
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Albany Medical Center
Albany, New York, 12208
Providence Alaska Medical Center
Anchorage, Alaska, 99508
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Mission Hospital
Asheville, North Carolina, 28801
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Eastern Maine Medical Center
Bangor, Maine, 04401
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
T C Thompson Children's Hospital
Chattanooga, Tennessee, 37403
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Nationwide Children's Hospital
Columbus, Ohio, 43205
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Medical City Dallas Hospital
Dallas, Texas, 75230
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Dayton Children's Hospital
Dayton, Ohio, 45404
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Kaiser Permanente Downey Medical Center
Downey, California, 90242
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Broward Health Medical Center
Fort Lauderdale, Florida, 33316
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Cook Children's Medical Center
Fort Worth, Texas, 76104
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
East Carolina University
Greenville, North Carolina, 27834
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Loma Linda University Medical Center
Loma Linda, California, 92354
Children's Hospital Los Angeles
Los Angeles, California, 90027
Cedars Sinai Medical Center
Los Angeles, California, 90048
Norton Children's Hospital
Louisville, Kentucky, 40202
UMC Cancer Center / UMC Health System
Lubbock, Texas, 79415
Valley Children's Hospital
Madera, California, 93636
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Loyola University Medical Center
Maywood, Illinois, 60153
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
Banner Children's at Desert
Mesa, Arizona, 85202
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Nicklaus Children's Hospital
Miami, Florida, 33155
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
USA Health Strada Patient Care Center
Mobile, Alabama, 36604
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Morristown Medical Center
Morristown, New Jersey, 07960
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
Mount Sinai Hospital
New York, New York, 10029
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Kaiser Permanente-Oakland
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital of Orange County
Orange, California, 92868
AdventHealth Orlando
Orlando, Florida, 32803
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Nemours Children's Hospital
Orlando, Florida, 32827
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Advocate Children's Hospital-Park Ridge
Park Ridge, Illinois, 60068
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Oregon Health and Science University
Portland, Oregon, 97239
Naval Medical Center - Portsmouth
Portsmouth, Virginia, 23708-2197
Rhode Island Hospital
Providence, Rhode Island, 02903
Carilion Children's
Roanoke, Virginia, 24014
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Primary Children's Hospital
Salt Lake City, Utah, 84113
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
Naval Medical Center -San Diego
San Diego, California, 92134
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Memorial Health University Medical Center
Savannah, Georgia, 31404
Maine Children's Cancer Program
Scarborough, Maine, 04074
Seattle Children's Hospital
Seattle, Washington, 98105
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Baystate Medical Center
Springfield, Massachusetts, 01199
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Stony Brook University Medical Center
Stony Brook, New York, 11794
State University of New York Upstate Medical University
Syracuse, New York, 13210
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
Madigan Army Medical Center
Tacoma, Washington, 98431
Tampa General Hospital
Tampa, Florida, 33606
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502
New York Medical College
Valhalla, New York, 10595
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Saint Mary's Hospital
West Palm Beach, Florida, 33407
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655
Australia8 sites
John Hunter Children's Hospital
Hunter Regional Mail Centre, New South Wales, 2310
Women's and Children's Hospital-Adelaide
North Adelaide, South Australia, 5006
Royal Children's Hospital
Parkville, Victoria, 3052
Princess Margaret Hospital for Children
Perth, Western Australia, 6008
Perth Children's Hospital
Perth, Western Australia, 6009
Sydney Children's Hospital
Randwick, New South Wales, 2031
Queensland Children's Hospital
South Brisbane, Queensland, 4101
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
Canada8 sites
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
Puerto Rico3 sites
HIMA San Pablo Oncologic Hospital
Caguas, 00726
San Jorge Children's Hospital
San Juan, 00912
University Pediatric Hospital
San Juan, 00926
New Zealand2 sites
Christchurch Hospital
Christchurch, 8011
Starship Children's Hospital
Grafton, Auckland, 1145
Saudi Arabia1 site
King Faisal Specialist Hospital and Research Centre
Riyadh, 11211
About this study
Official title: A Phase III Study for Patients With Newly Diagnosed Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide and All-Trans Retinoic Acid
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To eliminate exposure to conventional chemotherapy (including anthracyclines), for patients with standard risk acute promyelocytic leukemia (APL), through use of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) (tretinoin) based therapy while achieving an event free survival (EFS) that is not inferior compared to historical controls.
II. To significantly reduce exposure to conventional chemotherapy, and in particular, anthracycline exposure, for patients with high risk APL, through use of ATO and ATRA based therapy while achieving an event free survival that is not inferior compared to historical controls.
EXPLORATORY OBJECTIVES:
- To analyze the clinical impact of FMS-like tyrosine kinase 3 (FLT3) mutations in pediatric APL.
II. To correlate clinical outcomes with the kinetics of reduction in promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARalpha) transcript level by quantitative real-time (RT)-polymerase chain reaction (PCR) (RQ-PCR) in bone marrow and peripheral blood samples from diagnosis to time points during therapy.
III. To monitor incidence of coagulopathy complications, utilizing standardized conventional supportive care, and correlate with a battery of coagulation testing.
IV. To evaluate the neurocognitive outcomes of patients treated on this protocol using patient-completed, performance-based measures of neuropsychological functioning and parent questionnaire report.
OUTLINE:
INDUCTION THERAPY: Patients with standard and high risk APL receive tretinoin orally (PO) twice daily (BID) and arsenic trioxide intravenously (IV) over 2-4 hours on days 1-28. High risk APL patients also receive dexamethasone PO or IV BID on days 1-14 and idarubicin IV over 15 minutes on days 1, 3, 5, and 7. Patients achieving hematologic complete remission (hCR)/hematologic complete remission with incomplete blood count recovery (hCRi) may go on to consolidation therapy. Patients who do not achieve hCR/hCRi may continue treatment with tretinoin and arsenic trioxide for up to 70 days.
CONSOLIDATION THERAPY: Patients receive tretinoin PO BID on days 1-14 and 29-42 and arsenic trioxide IV over 2-4 hours on days 1-5, 8-12, 15-19, and 22-26. Treatment repeats every 56 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive tretinoin PO BID on days 1-14 and arsenic trioxide IV over 2-4 hours on days 1-5, 8-12, 15-19, and 22-26.
MINIMAL RESIDUAL DISEASE (MRD) CONSOLIDATION THERAPY: Patients who have APL in the bone marrow after 2 courses of consolidation therapy receive MRD consolidation therapy prior to continuing onto consolidation course 3. Patients receive cytarabine IV over 1-3 hours every 12 hours on days 1-4; mitoxantrone hydrochloride IV over 15-30 minutes on days 3-6; and tretinoin PO BID on days 1-14. If there are no APL cells in the bone marrow after completion of MRD consolidation therapy, patients continue on to consolidation course 3.
After completion of study treatment, patients are followed up monthly for 12 months, every 3 months for 36 months, every 6 months for 48 months, and then annually for 2 years.
- Being tested
- Arsenic Trioxide, Cytarabine, Dexamethasone, Idarubicin, Laboratory Biomarker Analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arsenic TrioxideDrug
Also called Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid, Arsenous Acid Anhydride
Given IV
CytarabineDrug
Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
Given IV
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO or IV
IdarubicinDrug
Also called 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin, 4-DMDR
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Mitoxantrone HydrochlorideDrug
Also called CL 232315, DHAD, DHAQ, Dihydroxyanthracenedione Dihydrochloride
Given IV
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
TretinoinDrug
Also called 2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-, Aberel, Airol, Aknoten
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (tretinoin, arsenic trioxide, chemotherapy) | Experimental | See Detailed Description Receives: Drug: Arsenic Trioxide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Idarubicin; Other: Laboratory Biomarker Analysis; Drug: Mitoxantrone Hydrochloride; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Tretinoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 24 months
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.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2015 (estimated)
- Study start21 Jul 2015
- Primary completion31 Oct 2020
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Promyelocytic Leukemia With t(15;17)(q24.1;q21.2); PML-RARAStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 158 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Matthew A Kutny, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02339740
- Sponsor's protocol ID
- AAML1331
- Other IDs
- NCI-2014-02266, PAAML1331_A01PAMDREVW0, AAML1331, AAML1331, AAML1331, U10CA180886
- Status last verified
- Feb 2026
- First submitted
- 13 Jan 2015
- Last updated
- 18 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive
Publications
Kutny MA, Alonzo TA, Abla O, Rajpurkar M, Gerbing RB, Wang YC, Hirsch BA, Raimondi S, Kahwash S, Hardy KK, Hardy S, Meshinchi S, Gamis AS, Kolb EA, Feusner JH, Gregory J Jr. Assessment of Arsenic Trioxide and All-trans Retinoic Acid for the Treatment of Pediatric Acute Promyelocytic Leukemia: A Report From the Children's Oncology Group AAML1331 Trial. JAMA Oncol. 2022 Jan 1;8(1):79-87. doi: 10.1001/jamaoncol.2021.5206.
PubMed 34762093
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Study for Patients With Newly Diagnosed Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide and All-Trans Retinoic Acid
- ClinicalTrials.gov ID
- NCT02339740
- Acronym / sponsor ID
- AAML1331
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 158 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 21 Jul 2015 (actual)
- Primary completion
- 31 Oct 2020 (actual)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 15 Jan 2015 (estimated)
- Results
- Posted 16 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To eliminate exposure to conventional chemotherapy (including anthracyclines), for patients with standard risk acute promyelocytic leukemia (APL), through use of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) (tretinoin) based therapy while achieving an event free survival (EFS) that is not inferior compared to historical controls.
II. To significantly reduce exposure to conventional chemotherapy, and in particular, anthracycline exposure, for patients with high risk APL, through use of ATO and ATRA based therapy while achieving an event free survival that is not inferior compared to historical controls.
EXPLORATORY OBJECTIVES:
- To analyze the clinical impact of FMS-like tyrosine kinase 3 (FLT3) mutations in pediatric APL.
II. To correlate clinical outcomes with the kinetics of reduction in promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARalpha) transcript level by quantitative real-time (RT)-polymerase chain reaction (PCR) (RQ-PCR) in bone marrow and peripheral blood samples from diagnosis to time points during therapy.
III. To monitor incidence of coagulopathy complications, utilizing standardized conventional supportive care, and correlate with a battery of coagulation testing.
IV. To evaluate the neurocognitive outcomes of patients treated on this protocol using patient-completed, performance-based measures of neuropsychological functioning and parent questionnaire report.
OUTLINE:
INDUCTION THERAPY: Patients with standard and high risk APL receive tretinoin orally (PO) twice daily (BID) and arsenic trioxide intravenously (IV) over 2-4 hours on days 1-28. High risk APL patients also receive dexamethasone PO or IV BID on days 1-14 and idarubicin IV over 15 minutes on days 1, 3, 5, and 7. Patients achieving hematologic complete remission (hCR)/hematologic complete remission with incomplete blood count recovery (hCRi) may go on to consolidation therapy. Patients who do not achieve hCR/hCRi may continue treatment with tretinoin and arsenic trioxide for up to 70 days.
CONSOLIDATION THERAPY: Patients receive tretinoin PO BID on days 1-14 and 29-42 and arsenic trioxide IV over 2-4 hours on days 1-5, 8-12, 15-19, and 22-26. Treatment repeats every 56 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive tretinoin PO BID on days 1-14 and arsenic trioxide IV over 2-4 hours on days 1-5, 8-12, 15-19, and 22-26.
MINIMAL RESIDUAL DISEASE (MRD) CONSOLIDATION THERAPY: Patients who have APL in the bone marrow after 2 courses of consolidation therapy receive MRD consolidation therapy prior to continuing onto consolidation course 3. Patients receive cytarabine IV over 1-3 hours every 12 hours on days 1-4; mitoxantrone hydrochloride IV over 15-30 minutes on days 3-6; and tretinoin PO BID on days 1-14. If there are no APL cells in the bone marrow after completion of MRD consolidation therapy, patients continue on to consolidation course 3.
After completion of study treatment, patients are followed up monthly for 12 months, every 3 months for 36 months, every 6 months for 48 months, and then annually for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (tretinoin, arsenic trioxide, chemotherapy) | Experimental | Drug: Arsenic Trioxide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Idarubicin, Other: Laboratory Biomarker Analysis, Drug: Mitoxantrone Hydrochloride, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Drug: TretinoinSee Detailed Description |
Who may qualify
- Ages
- 12 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Patients must be newly diagnosed with a clinical diagnosis of APL (initially by morphology of bone marrow or peripheral blood)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arsenic TrioxideAlso: Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid, Arsenous Acid AnhydrideGiven IV | Drug | Treatment (tretinoin, arsenic trioxide, chemotherapy) |
| CytarabineAlso: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinoneGiven IV | Drug | Treatment (tretinoin, arsenic trioxide, chemotherapy) |
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO or IV | Drug | Treatment (tretinoin, arsenic trioxide, chemotherapy) |
| IdarubicinAlso: 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin, 4-DMDRGiven IV | Drug | Treatment (tretinoin, arsenic trioxide, chemotherapy) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (tretinoin, arsenic trioxide, chemotherapy) |
| Mitoxantrone HydrochlorideAlso: CL 232315, DHAD, DHAQ, Dihydroxyanthracenedione DihydrochlorideGiven IV | Drug | Treatment (tretinoin, arsenic trioxide, chemotherapy) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (tretinoin, arsenic trioxide, chemotherapy) |
| Questionnaire AdministrationAncillary studies | Other | Treatment (tretinoin, arsenic trioxide, chemotherapy) |
| TretinoinAlso: 2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-, Aberel, Airol, AknotenGiven PO | Drug | Treatment (tretinoin, arsenic trioxide, chemotherapy) |
Primary outcome
Event-free Survival (EFS) in Standard Risk Acute Promyelocytic Leukemia (APL) Patients
Time frame: Up to 24 months
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.
EFS in High Risk APL Patients
Time frame: Up to 24 months
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34762093Kutny MA, Alonzo TA, Abla O, Rajpurkar M, Gerbing RB, Wang YC, Hirsch BA, Raimondi S, Kahwash S, Hardy KK, Hardy S, Meshinchi S, Gamis AS, Kolb EA, Feusner JH, Gregory J Jr. Assessment of Arsenic Trioxide and All-trans Retinoic Acid for the Treatment of Pediatric Acute Promyelocytic Leukemia: A Report From the Children's Oncology Group AAML1331 Trial. JAMA Oncol. 2022 Jan 1;8(1):79-87. doi: 10.1001/jamaoncol.2021.5206.
- Individual participant dataSharing planned: Yes. Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew A Kutny principal investigator
Children's Oncology Group
174 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Arsenic Trioxide, Cytarabine and Dexamethasone in people with Acute Promyelocytic Leukemia With t(15;17)(q24.1;q21.2); PML-RARA, run by Children's Oncology Group at 174 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 174 sites in United States, Australia, Canada, Puerto Rico, New Zealand and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free Survival (EFS) in Standard Risk Acute Promyelocytic Leukemia (APL) Patients (time frame: Up to 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02339740, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2026.