Acute Lymphoblastic LeukemiaPhase 2/3NCT00720109
Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
A Phase 2/3 study testing Asparaginase, Cyclophosphamide and Cytarabine in people with Acute Lymphoblastic Leukemia and Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, run by National Cancer Institute (NCI) at 134 sites in 5 countries.
Trial summary
This phase II/III trial is studying the side effects and how well giving dasatinib together with combination chemotherapy works in treating young patients with newly diagnosed acute lymphoblastic leukemia (ALL). Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 2 to 30 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
- What is being tested?
- Asparaginase, Cyclophosphamide and Cytarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 134 sitesin 5 countries
- Study dates
- 14 Jul 2008to 31 Mar 2020
- Phase
- Phase 2/3
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 2 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Newly diagnosed acute lymphoblastic leukemia (ALL)
- Definitive evidence of BCR-ABL fusion (Philadelphia chromosome positive [PH+]) from an approved Children's Oncology Group (COG) cytogenetics laboratory
- Meets one of the following criteria:
- Concurrent enrollment on Clusters of Orthologous Groups (COG)-AALL03B1 (or a successor trial) AND COG-AALL0232, COG-AALL0331, COG-AALL0434 or other front-line COG ALL clinical trial
- Concurrent enrollment on COG-AALL03B1 (or a successor trial) AND scheduled to receive a 3 or 4-drug standard induction regimen
- Concurrent enrollment on a Dana-Farber Cancer Institute (DFCI) Childhood ALL Consortium trial (or scheduled to be treated as per a DFCI Childhood ALL Consortium induction regimen)
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- All patients must have definitive evidence of BCR-ABL fusion from an approved COG cytogenetics laboratory; patients may NOT have received Day 15 of Induction chemotherapy (or day 18 vincristine if enrolled on a DFCI Childhood ALL Consortium trial) prior to enrollment on AALL0622
- Patients must have a performance status of 0, 1 or 2 at completion of two weeks of Induction; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73 m^2 or maximum serum creatinine based on age and gender as follows:
- 0.4 mg/dL (for patients 1 to 5 months of age)
- 0.5 mg/dL (for patients 6 to 11 months of age)
- 0.6 mg/dL (for patients 1 year of age)
- 0.8 mg/dL (for patients 2 to 5 years of age)
- 1.0 mg/dL (for patients 6 to 9 years of age)
- 1.2 mg/dL (for patients 10 to 12 years of age)
- 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
- 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age)
- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 times ULN for age
- Shortening fraction >= 27% by echocardiogram or ejection fraction >= 50% by gated radionuclide study
- No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% at sea level if there is clinical indication for determination
- Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled; however, drugs that induce CYP3A4/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, phenobarbital) should be avoided
- Patients will start AALL0622 therapy on day 15 of induction therapy (or day 18 if enrolled on a DFCI Childhood ALL Consortium trial); patients must have received the first 2 weeks of Induction therapy
Who cannot join
- Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method
- Female patients who are lactating must agree to stop breast-feeding
- Patients with Down syndrome
- Patients with any clinically significant cardiovascular disease including the following:
- Myocardial infarction or ventricular tachyarrhythmia within 6 months
- Ejection fraction less than institutional normal
- Major conduction abnormality (unless a cardiac pacemaker is present)
Trial locations and contacts
134 sites in 5 countries.
134 sites in 5 countries
United States118 sites
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102
Texas Tech University Health Sciences Center-Amarillo
Amarillo, Texas, 79106
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Children's Hospital of Alabama
Birmingham, Alabama, 35233
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Saint Luke's Mountain States Tumor Institute
Boise, Idaho, 83712
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
West Virginia University Charleston Division
Charleston, West Virginia, 25304
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Missouri - Ellis Fischel
Columbia, Missouri, 65212
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
Geisinger Medical Center
Danville, Pennsylvania, 17822
Dayton Children's Hospital
Dayton, Ohio, 45404
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Kaiser Permanente Downey Medical Center
Downey, California, 90242
Michigan State University Clinical Center
East Lansing, Michigan, 48824-7016
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
University of Connecticut
Farmington, Connecticut, 06030
Lee Memorial Health System
Fort Myers, Florida, 33901
Cook Children's Medical Center
Fort Worth, Texas, 76104
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, 49503
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, 49503
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Riley Hospital for Children
Indianapolis, Indiana, 46202
Saint Vincent Hospital and Health Care Center
Indianapolis, Indiana, 46260
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Kalamazoo Center for Medical Studies
Kalamazoo, Michigan, 49008
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, 89106
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Mattel Children's Hospital UCLA
Los Angeles, California, 90095
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
Norton Children's Hospital
Louisville, Kentucky, 40202
Valley Children's Hospital
Madera, California, 93636
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Loyola University Medical Center
Maywood, Illinois, 60153
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Yale University
New Haven, Connecticut, 06520
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
NYP/Weill Cornell Medical 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 Christ Medical Center
Oak Lawn, Illinois, 60453-2699
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453
Kaiser Permanente-Oakland
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
Children's Hospital of Orange County
Orange, California, 92868
AdventHealth Orlando
Orlando, Florida, 32803
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806
UF Cancer Center at Orlando Health
Orlando, Florida, 32806
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Sacred Heart Hospital
Pensacola, Florida, 32504
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Legacy Emanuel Hospital and Health Center
Portland, Oregon, 97227
Oregon Health and Science University
Portland, Oregon, 97239
Rhode Island Hospital
Providence, Rhode Island, 02903
Mayo Clinic
Rochester, Minnesota, 55905
Primary Children's Hospital
Salt Lake City, Utah, 84113
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
UCSF Medical Center-Mount Zion
San Francisco, California, 94115
UCSF Medical Center-Parnassus
San Francisco, California, 94143
Memorial Health University Medical Center
Savannah, Georgia, 31404
Seattle Children's Hospital
Seattle, Washington, 98105
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Washington University School of Medicine
St Louis, Missouri, 63110
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Overlook Hospital
Summit, New Jersey, 07902
State University of New York Upstate Medical University
Syracuse, New York, 13210
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Scott and White Memorial Hospital
Temple, Texas, 76508
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
Mercy Children's Hospital
Toledo, Ohio, 43608
Harbor-University of California at Los Angeles Medical Center
Torrance, California, 90502
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
New York Medical College
Valhalla, New York, 10595
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
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655
Canada9 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
Centre Hospitalier Universitaire de Quebec
Québec, G1V 4G2
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
Australia4 sites
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
Royal Children's Hospital-Brisbane
Herston, Queensland, 4029
Women's and Children's Hospital-Adelaide
North Adelaide, South Australia, 5006
Princess Margaret Hospital for Children
Perth, Western Australia, 6008
New Zealand2 sites
Christchurch Hospital
Christchurch, 8011
Starship Children's Hospital
Grafton, Auckland, 1145
About this study
Official title: Intensified Tyrosine Kinase Inhibitor Therapy (Dasatinib NSC# 732517) in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (ALL)
This phase II/III trial is studying the side effects and how well giving dasatinib together with combination chemotherapy works in treating young patients with newly diagnosed acute lymphoblastic leukemia (ALL). Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with combination chemotherapy may kill more cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the feasibility and toxicity of an intensified chemotherapeutic regimen that incorporates dasatinib for treatment of children, adolescents, and young adults (up to age 30) with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL).
II. To determine whether the intensification of tyrosine kinase inhibition through the addition of dasatinib in Induction (Days 15-28) and substitution of dasatinib for imatinib during post-Induction therapy, in the context of intensive cytotoxic therapy (according to AALL0031) and a good early response to therapy, will lead to a 3-year event-free survival (EFS) of at least 60% in patients with Ph+ ALL.
SECONDARY OBJECTIVES:
- To determine whether the addition of dasatinib during Induction therapy (Days 15-28) will decrease levels of minimal residual disease (MRD) present at end of Induction therapy as compared with COG AALL0031.
II. To determine whether early intensified tyrosine kinase inhibitor (TKI) therapy will lower end-Consolidation MRD levels as compared to patients on COG AALL0031 that received imatinib in Consolidation Blocks 1 and 2 (Cohorts 3-5).
III. To determine the overall 3-year EFS rate for the whole cohort of Standard- and High-Risk patients treated with dasatinib.
IV. To determine the long-term effects of dasatinib on growth, development, and bone metabolism.
- To assess BCR-ABL mutation status at time of diagnosis and progression/relapse.
OUTLINE: This is a multicenter study. Patients are stratified according to risk (standard risk vs high risk) at the end of consolidation therapy.
INDUCTION THERAPY (weeks 1-4): Patients receive initial induction therapy on days 1-14 prior to beginning the study. Patients then receive vincristine intravenously (IV) and daunorubicin hydrochloride* IV over 15 minutes on days 15 and 22; dasatinib orally (PO) once daily (QD) and prednisone PO (or methylprednisolone IV) twice daily (BID) on days 15-28; methotrexate intrathecally (IT) on day 29; and some patients receive methotrexate, hydrocortisone, and cytarabine IT on days 15 and 22. After completion of induction therapy, patients undergo bone marrow aspiration for evaluation of disease. Patients with M1 bone marrow and minimal residual disease (MRD) < 1% (standard-risk disease) proceed to block 1 consolidation therapy 1 week after completion of induction therapy or when blood counts recover (whichever occurs later). Patients with M2 or M3 bone marrow or MRD >= 1% (high-risk disease) proceed immediately to block 1 consolidation therapy, regardless of blood counts. Patients with clinically evident or biopsy-proven testicular leukemia at diagnosis that persists at the end of induction therapy undergo 12 fractions of testicular radiotherapy beginning within 4 days prior to starting block 1 consolidation therapy.
NOTE: *Patients who receive initial induction therapy on a DFCI Childhood ALL Consortium trial do not receive daunorubicin hydrochloride during induction therapy on this study.
CONSOLIDATION THERAPY:
BLOCK 1 CONSOLIDATION THERAPY: (weeks 6-8) Patients receive etoposide IV over 1 hour and ifosfamide IV over 1 hour on days 1-5, dasatinib PO on days 1-14 OR on days 1-21, and some patients receive methotrexate, hydrocortisone, and cytarabine IT on days 8 and 15. Patients also receive filgrastim (G-CSF) subcutaneously (SC) or IV QD beginning on day 6 and continuing until blood counts recover.
After completion of block 1 consolidation therapy, patients proceed to block 2 consolidation therapy.
BLOCK 2 CONSOLIDATION THERAPY: (weeks 9-11) Patients receive high-dose methotrexate IV continuously over 24 hours on day 1; leucovorin calcium PO or IV every 6 hours for 3 doses on days 2-3; methotrexate, hydrocortisone, and cytarabine IT on day 1; cytarabine IV over 3 hours every 12 hours for 4 doses on days 2 and 3; and dasatinib PO on days 1-14 OR on days 1-21. Patients also receive G-CSF SC or IV QD beginning on day 4 and continuing until blood counts recover. After completion of block 2 consolidation therapy and recovery of blood counts, patients undergo bone marrow aspiration for evaluation of disease. Patients with MRD < 0.01% (standard-risk disease) with a matched related donor and who are willing to undergo hematopoietic stem cell transplantation (HSCT) proceed to HSCT off study. Standard-risk patients without a suitable donor or those who elect not to undergo HSCT proceed to post-consolidation therapy. Patients with MRD >= 0.01% (high-risk disease) with a matched related or unrelated donor proceed to HSCT off study. High-risk patients without a suitable donor proceed to post-consolidation therapy.
POST-CONSOLIDATION THERAPY:
REINDUCTION BLOCK 1 THERAPY: (weeks 12-14) Patients receive vincristine IV on days 1, 8, and 15; daunorubicin hydrochloride IV over 15 minutes on days 1 and 2; cyclophosphamide IV over 1 hour every 12 hours for 4 doses on days 3 and 4; pegaspargase intramuscularly (IM) on day 4; methotrexate, hydrocortisone, and cytarabine IT on days 1 and 15; dexamethasone PO or IV BID on days 1-7 and 15-21; and dasatinib PO on days 1-14 OR on days 1-21. Patients also receive G-CSF SC or IV QD beginning on day 5 and continuing until blood counts recover.
After completion of reinduction block 1 therapy, patients proceed to intensification block 1 therapy.
INTENSIFICATION BLOCK 1 THERAPY: (weeks 15-23) Patients receive high-dose methotrexate IV continuously over 24 hours on day 1; leucovorin calcium PO or IV every 6 hours for 3 doses on days 2-3; methotrexate, hydrocortisone, and cytarabine IT on days 1 and 22; etoposide IV over 1 hour and cyclophosphamide IV over 1 hour on days 22-26; cytarabine IV over 3 hours every 12 hours for 4 doses on days 43 and 44; asparaginase IM on day 44; and dasatinib PO on days 1-14, 22-35, and 43-56 OR on days 1-63. Patients also receive G-CSF SC or IV QD beginning on day 27 and continuing until blood counts recover. After completion of intensification block 1 therapy, patients proceed to reinduction block 2 therapy.
REINDUCTION BLOCK 2 THERAPY: (weeks 24-26) Patients receive reinduction block 2 therapy as per reinduction block 1 therapy. After completion of reinduction block 2 therapy, patients proceed to intensification block 2 therapy.
INTENSIFICATION BLOCK 2 THERAPY: (weeks 27-35) Patients receive intensification block 2 therapy as per intensification block 1 therapy. After completion of intensification block 2 therapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY:
MAINTENANCE COURSES 1-4: (weeks 36-67) Patients receive high-dose methotrexate IV continuously over 24 hours on day 1; leucovorin calcium PO or IV every 6 hours for 3 doses on days 2-3; methotrexate, hydrocortisone, and cytarabine IT and vincristine IV on days 1 and 29; prednisone PO or IV BID on days 1-5 and 29-33; mercaptopurine PO on days 8-28; methotrexate PO on days 8, 15, and 22; etoposide IV over 1 hour and cyclophosphamide IV over 1 hour on days 29-33; and dasatinib PO on days 1-14 and 29-42 OR on days 1-56. Patients also receive G-CSF SC or IV QD beginning on day 34 and continuing until blood counts recover. Courses repeat every 56 days. After completion of maintenance courses 1-4, patients proceed to maintenance course 5.
MAINTENANCE COURSE 5: (weeks 68-75) Patients receive vincristine IV on days 1 and 29; prednisone PO or IV BID on maintenance courses 6-12.
MAINTENANCE COURSES 6-12: (weeks 76-131) Patients receive vincristine IV on days 1 and 29; prednisone PO or IV BID on days 1-5 and 29-33; mercaptopurine PO on days 1-56; methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, and 50; and dasatinib PO on days 1-14 and 29-42 OR on days 1-56.
Courses repeat every 56 days. Patients long-term growth, development, and bone metabolism are assessed after completion of study therapy and then annually for 5 years.
After completion of study therapy, patients are followed up periodically for up to 10 years.
- Conditions
- Acute Lymphoblastic Leukemia, Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
- Being tested
- Asparaginase, Cyclophosphamide, Cytarabine, Dasatinib, Daunorubicin Hydrochloride
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AsparaginaseDrug
Also called ASP-1, Asparaginase II, Asparaginase-E.Coli, Colaspase
Given IT
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
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 IT or IV
DasatinibDrug
Also called BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel
Given PO
Daunorubicin HydrochlorideDrug
Also called Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin
Given IV
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given IV or PO
EtoposideDrug
Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar
Given IV
FilgrastimBiological
Also called G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
Given IV or SC
Hydrocortisone Sodium SuccinateDrug
Also called (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt, A-Hydrocort, Buccalsone, Corlan
Given IT
IfosfamideDrug
Also called Asta Z 4942, Asta Z-4942, Cyfos, Holoxan
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate
Given IV or PO
MercaptopurineDrug
Also called 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine
Given PO
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IT, PO, or IV
Also called Adlone, Caberdelta M, DepMedalone, Depo Moderin
Given IV
PegaspargaseDrug
Also called L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-asparaginase
Given IM
PrednisoneDrug
Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl
Given PO or IV
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Irradiate, Irradiated, irradiation
Some patients undergo cranial RT
Also called Kyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor therapy and chemotherapy) | Experimental | See Detailed Description Receives: Drug: Asparaginase; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dasatinib; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Etoposide; Biological: Filgrastim; Drug: Hydrocortisone Sodium Succinate; Drug: Ifosfamide; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Pegaspargase; Drug: Prednisone; Radiation: Radiation Therapy; Drug: Vincristine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-Free Survival (EFS) of Patients With Standard-risk Disease Treated With Dasatinib in Combination With Intensified Chemotherapy
Event-Free Survival (EFS) curves will be constructed using the Kaplan-Meier life table method with standard errors computed using the method of Peto and Peto. A 1-sided 95% confidence interval for EFS will be constructed.
Measured: At 3 years
Feasibility and Toxicity of an Intensified Chemotherapeutic Regimen Incorporating Dasatinib for Treatment of Children and Adolescents With Ph+ ALL Assessed by Examining Adverse Events
Number of patients in safety cohort with dose limiting toxicity (DLT)(including treatment delay)
Measured: Weeks 3 through 23 of treatment (From week 3 Induction through Intensification Block 1)
Secondary outcomes (3)
Contribution of Dasatinib on Minimal Residual Disease (MRD) After Induction Therapy
Percent of patients MRD Positive (MRD > 0.01%) at End of Induction.
Measured: At the end of induction therapy (at 5 weeks)
Percent of Patients MRD Positive (MRD > 0.01%) at End of Consolidation
A 1-sample Z-test of proportions (alpha=5%, 1-sided test) will be used.
Measured: At end of consolidation (at 11 weeks)
Overall EFS Rate for the Combined Cohort of Standard- and High-Risk Patients (Who Receive the Final Chosen Dose of Dasatinib)
An event is defined as: Induction failure, relapse at any site, secondary malignancy, or death.
Measured: From the time entry on study to first event or date of last follow-up, assessed up to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2008 (estimated)
- Study start14 Jul 2008
- Primary completion31 Dec 2014
- Study completion31 Mar 2020
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 (2)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- William B Slayton, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00720109
- Sponsor's protocol ID
- NCI-2009-00312
- Other IDs
- NCI-2009-00312, AALL0622, CDR0000600217, 08-829, COG-AALL0622, AALL0622, AALL0622, U10CA098543
- Status last verified
- Apr 2020
- First submitted
- 19 Jul 2008
- Last updated
- 13 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Tasian SK, Peters C. Targeted therapy or transplantation for paediatric ABL-class Ph-like acute lymphocytic leukaemia? Lancet Haematol. 2020 Dec;7(12):e858-e859. doi: 10.1016/S2352-3026(20)30369-0. No abstract available.
PubMed 33242441Slayton WB, Schultz KR, Kairalla JA, Devidas M, Mi X, Pulsipher MA, Chang BH, Mullighan C, Iacobucci I, Silverman LB, Borowitz MJ, Carroll AJ, Heerema NA, Gastier-Foster JM, Wood BL, Mizrahy SL, Merchant T, Brown VI, Sieger L, Siegel MJ, Raetz EA, Winick NJ, Loh ML, Carroll WL, Hunger SP. Dasatinib Plus Intensive Chemotherapy in Children, Adolescents, and Young Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Results of Children's Oncology Group Trial AALL0622. J Clin Oncol. 2018 Aug 1;36(22):2306-2314. doi: 10.1200/JCO.2017.76.7228. Epub 2018 May 29.
PubMed 29812996