CompletedNCT00720109Updated Apr 13, 2020Results posted

Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

A Phase 2/3 interventional study of Asparaginase and Cyclophosphamide in Acute Lymphoblastic Leukemia, Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 and Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, sponsored by National Cancer Institute (NCI). Completed at 134 sites in 5 countries. Open to participants aged 2 Years to 30 Years. Per ClinicalTrials.gov, last updated 2020-04-13.

Sponsored by National Cancer Institute (NCI) · Phase 2/3, Interventional, and Treatment

Phase: Phase 2/3
Study type: Interventional
Enrollment: 63
Allocation: Not applicable
Ages: 2 Years to 30 Years
Sex: All

Study 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. 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:

I. 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:

I. 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.

V. 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 studied

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

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In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 63 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.

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Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 2 Years to 30 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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)
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

Exclusion criteria

Exclusion Criteria:

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)

Study design

Phase: Phase 2 / Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 63 participants (actual)

Study arms

Experimental
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
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

Interventions

DrugAsparaginase
Given IT
Also known as: ASP-1, Asparaginase II, Asparaginase-E.Coli, Colaspase, Elspar, Kidrolase, L-Asnase, L-ASP, L-asparaginase, L-Asparagine amidohydrolase, Laspar, Lcf-ASP, Leucogen, Leunase, MK-965, Paronal, Re-82-TAD-15, Serasa, Spectrila
DrugCyclophosphamide
Given IV
Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
DrugCytarabine
Given IT or IV
Also known as: .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, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453
DrugDasatinib
Given PO
Also known as: BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel
DrugDaunorubicin Hydrochloride
Given IV
Also known as: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilem
DrugDexamethasone
Given IV or PO
Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex
DrugEtoposide
Given IV
Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16
BiologicalFilgrastim
Given IV or SC
Also known as: G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim
DrugHydrocortisone Sodium Succinate
Given IT
Also known as: (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt, A-Hydrocort, Buccalsone, Corlan, Cortisol sodium succinate, Cortop, Efcortelan, Emergent-EZ, Flebocortid, Hidroc Clora, Hycorace, Hydro-Adreson, Hydrocort, Hydrocortisone 21-Sodium Succinate, Hydrocortisone Na Succinate, Kinogen, Nordicort, Nositrol, Sinsurrene, Sodium hydrocortisone succinate, Solu-Cortef, Solu-Glyc
DrugIfosfamide
Given IV
Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942
OtherLaboratory Biomarker Analysis
Correlative studies
DrugLeucovorin Calcium
Given IV or PO
Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, citrovorum factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin
DrugMercaptopurine
Given PO
Also known as: 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine, 6-Mercaptopurine, 6-Mercaptopurine Monohydrate, 6-MP, 6-Purinethiol, 6-Thiopurine, 6-Thioxopurine, 6H-Purine-6-thione, 1,7-dihydro- (9CI), 7-Mercapto-1,3,4,6-tetrazaindene, Alti-Mercaptopurine, Azathiopurine, BW 57-323H, Flocofil, Ismipur, Leukerin, Leupurin, Mercaleukim, Mercaleukin, Mercaptina, Mercaptopurinum, Mercapurin, Mern, NCI-C04886, Puri-Nethol, Purimethol, Purine, 6-mercapto-, Purine-6-thiol (8CI), Purine-6-thiol, monohydrate, Purinethiol, Purinethol, U-4748, WR-2785
DrugMethotrexate
Given IT, PO, or IV
Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039
DrugMethylprednisolone
Given IV
Also known as: Adlone, Caberdelta M, DepMedalone, Depo Moderin, Depo-Nisolone, Duralone, Emmetipi, Esametone, Firmacort, Medlone 21, Medrate, Medrol, Medrol Veriderm, Medrone, Mega-Star, Meprolone, Methylprednisolonum, Metilbetasone Solubile, Metrocort, Metypresol, Metysolon, Predni-M-Tablinen, Prednilen, Radilem, Sieropresol, Solpredone, Summicort, Urbason, Veriderm Medrol, Wyacort
DrugPegaspargase
Given IM
Also known as: L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-asparaginase, PEG-L-Asparaginase, PEG-L-Asparaginase (Enzon - Kyowa Hakko), PEGLA, Polyethylene Glycol L-Asparaginase, Polyethylene Glycol-L-Asparaginase
DrugPrednisone
Given PO or IV
Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone
RadiationRadiation Therapy
Some patients undergo cranial RT
Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
DrugVincristine Sulfate
Given IV
Also known as: Kyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

What researchers measure

Primary outcomes

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.
Time frame: 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)
Time frame: Weeks 3 through 23 of treatment (From week 3 Induction through Intensification Block 1)

Secondary outcomes

Contribution of Dasatinib on Minimal Residual Disease (MRD) After Induction Therapy
Percent of patients MRD Positive (MRD \> 0.01%) at End of Induction.
Time frame: 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.
Time frame: 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.
Time frame: From the time entry on study to first event or date of last follow-up, assessed up to 7 years

Results

Posted Oct 7, 2016

Participant flow

Induction Period

Participant flow — Induction Period
Milestone	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)	Standard-risk	High-risk
Started	63	0	0
Completed	57	0	0
Not completed	6	0	0
Withdrew: Did not meet eligibility criteria	3	0	0
Withdrew: Bone marrow transplant	2	0	0
Withdrew: Physician decision	1	0	0

Risk Stratification Period

Participant flow — Risk Stratification Period
Milestone	Standard-risk	High-risk
Started	48	9
Completed	33	1
Not completed	15	8
Withdrew: Adverse event	1	0
Withdrew: Physician decision	2	1
Withdrew: Bone marrow transplant	9	7
Withdrew: Disease progression or relapse	2	0
Withdrew: Development of second malignant neoplasm	1	0

Outcome measures

PrimaryEvent-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.

Time frame:: At 3 years
Reported as:: Number · Percent probability

Event-Free Survival (EFS) of Patients With Standard-risk Disease Treated With Dasatinib in Combination With Intensified Chemotherapy
Percent probability	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)	Standard-risk	High-risk
Event-Free Survival (EFS) of Patients With Standard-risk Disease Treated With Dasatinib in Combination With Intensified Chemotherapy	79.8 (71.1 to 88.5)	83.2 (74.1 to 92.2)	66.7 (40.9 to 92.5)

PrimaryFeasibility 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)

Time frame:: Weeks 3 through 23 of treatment (From week 3 Induction through Intensification Block 1)
Reported as:: Number · Pts with DLTs

Feasibility and Toxicity of an Intensified Chemotherapeutic Regimen Incorporating Dasatinib for Treatment of Children and Adolescents With Ph+ ALL Assessed by Examining Adverse Events
Pts with DLTs	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)
Feasibility and Toxicity of an Intensified Chemotherapeutic Regimen Incorporating Dasatinib for Treatment of Children and Adolescents With Ph+ ALL Assessed by Examining Adverse Events	1

SecondaryContribution of Dasatinib on Minimal Residual Disease (MRD) After Induction Therapy

Percent of patients MRD Positive (MRD \> 0.01%) at End of Induction.

Time frame:: At the end of induction therapy (at 5 weeks)
Reported as:: Number · Percentage of participants

Contribution of Dasatinib on Minimal Residual Disease (MRD) After Induction Therapy
Percentage of participants	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)	Standard-risk	High-risk
Contribution of Dasatinib on Minimal Residual Disease (MRD) After Induction Therapy	40.7 (30.8 to 51.4)	29.2 (19.7 to 40.9)	100.0 (73.1 to 100.0)

Statistical analysis

Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) · Chi-squared · p = <0.001 · Percentage: 40.7 · 90% CI 30.8 to 51.4Chi-squared test equivalent to Z-test of proportions.

SecondaryPercent 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.

Time frame:: At end of consolidation (at 11 weeks)
Reported as:: Number · Percentage of participants

Percent of Patients MRD Positive (MRD > 0.01%) at End of Consolidation
Percentage of participants	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)	Standard-risk	High-risk
Percent of Patients MRD Positive (MRD > 0.01%) at End of Consolidation	10.5 (5.3 to 19.3)	0 (0.0 to 6.4)	66.7 (39.6 to 96.1)

Statistical analysis

Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) · Binomial Test · p = =0.13 · Percentage: 10.5 · 90% CI 5.3 to 19.3The pre-specified threshold for the estimated percentage of MRD positivity at End Consolidation was set to 16%. Results show an upper bound on the (Agresti-Coull) confidence interval of 19.3%.

SecondaryOverall 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.

Time frame:: From the time entry on study to first event or date of last follow-up, assessed up to 7 years
Reported as:: Number · percentage of patients

Overall EFS Rate for the Combined Cohort of Standard- and High-Risk Patients (Who Receive the Final Chosen Dose of Dasatinib)
percentage of patients	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)	Standard-risk	High-risk
Overall EFS Rate for the Combined Cohort of Standard- and High-Risk Patients (Who Receive the Final Chosen Dose of Dasatinib)	79.8 (71.1 to 88.5)	83.2 (74.1 to 92.2)	66.7 (40.9 to 92.5)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)	—	36/60 (60%)	59/60 (98.3%)
Standard-risk	—	28/48 (58.3%)	48/48 (100%)
High-risk	—	7/9 (77.8%)	8/9 (88.9%)

Most frequent serious events

Showing 10 of 77

Most frequent serious events
Event	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)	Standard-risk	High-risk
Alanine aminotransferase increasedInvestigations	16/60	11/48	5/9
Aspartate aminotransferase increasedInvestigations	9/60	6/48	3/9
HypokalemiaMetabolism and nutrition disorders	9/60	6/48	3/9
HypoalbuminemiaMetabolism and nutrition disorders	5/60	3/48	2/9
Infections and infestations - Other, specifyInfections and infestations	7/60	4/48	2/9
AgitationPsychiatric disorders	2/60	1/48	1/9
Allergic reactionImmune system disorders	1/60	0/48	1/9
AnemiaBlood and lymphatic system disorders	3/60	2/48	1/9
ConfusionPsychiatric disorders	2/60	1/48	1/9
Creatinine increasedInvestigations	2/60	1/48	1/9

Most frequent other events

Showing 10 of 124

Most frequent other events
Event	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)	Standard-risk	High-risk
Neutrophil count decreasedInvestigations	41/60	38/48	2/9
Febrile neutropeniaBlood and lymphatic system disorders	41/60	36/48	4/9
Infections and infestations - Other, specifyInfections and infestations	37/60	34/48	2/9
Alanine aminotransferase increasedInvestigations	31/60	29/48	2/9
Platelet count decreasedInvestigations	33/60	29/48	3/9
HypokalemiaMetabolism and nutrition disorders	29/60	27/48	1/9
White blood cell decreasedInvestigations	24/60	20/48	3/9
AnemiaBlood and lymphatic system disorders	23/60	19/48	3/9
Aspartate aminotransferase increasedInvestigations	20/60	19/48	1/9
HyperglycemiaMetabolism and nutrition disorders	13/60	10/48	3/9

Baseline characteristics

Since all patients were enrolled under induction therapy and later risk stratified, all patients are grouped under the treatment induction group, including the three ineligible patients.

Age, Categorical
Age, Categorical(Participants)	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)
<=18 years	56
Between 18 and 65 years	7
>=65 years	0

Sex: Female, Male
Sex: Female, Male(Participants)	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)
Female	20
Male	43

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)
Hispanic or Latino	10
Not Hispanic or Latino	52
Unknown or Not Reported	1

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy)
American Indian or Alaska Native	2
Asian	3
Native Hawaiian or Other Pacific Islander	1
Black or African American	9
White	45
More than one race	3
Unknown or Not Reported	0

Study locations

134 sites

Children's Hospital of Alabama
Birmingham, Alabama 35233, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233, United States
Phoenix Childrens Hospital
Phoenix, Arizona 85016, United States
Banner University Medical Center - Tucson
Tucson, Arizona 85719, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205, United States
Kaiser Permanente Downey Medical Center
Downey, California 90242, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California 90806, United States
Children's Hospital Los Angeles
Los Angeles, California 90027, United States
Mattel Children's Hospital UCLA
Los Angeles, California 90095, United States
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California 90095, United States
Valley Children's Hospital
Madera, California 93636, United States
Kaiser Permanente-Oakland
Oakland, California 94611, United States
Children's Hospital of Orange County
Orange, California 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California 94304, United States
Rady Children's Hospital - San Diego
San Diego, California 92123, United States
UCSF Medical Center-Mount Zion
San Francisco, California 94115, United States
UCSF Medical Center-Parnassus
San Francisco, California 94143, United States
Harbor-University of California at Los Angeles Medical Center
Torrance, California 90502, United States
Children's Hospital Colorado
Aurora, Colorado 80045, United States
University of Connecticut
Farmington, Connecticut 06030, United States
Connecticut Children's Medical Center
Hartford, Connecticut 06106, United States
Yale University
New Haven, Connecticut 06520, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware 19803, United States
Children's National Medical Center
Washington, District of Columbia 20010, United States
Lee Memorial Health System
Fort Myers, Florida 33901, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida 32610, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida 32207, United States
AdventHealth Orlando
Orlando, Florida 32803, United States
Nemours Children's Clinic - Orlando
Orlando, Florida 32806, United States
UF Cancer Center at Orlando Health
Orlando, Florida 32806, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida 32504, United States
Sacred Heart Hospital
Pensacola, Florida 32504, United States
Johns Hopkins All Children's Hospital
Saint Petersburg, Florida 33701, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida 33607, United States
Saint Mary's Hospital
West Palm Beach, Florida 33407, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia 30322, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322, United States
Memorial Health University Medical Center
Savannah, Georgia 31404, United States
University of Hawaii Cancer Center
Honolulu, Hawaii 96813, United States
Saint Luke's Mountain States Tumor Institute
Boise, Idaho 83712, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois 60611, United States
University of Illinois
Chicago, Illinois 60612, United States
Loyola University Medical Center
Maywood, Illinois 60153, United States
Advocate Christ Medical Center
Oak Lawn, Illinois 60453-2699, United States
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois 60453, United States
Southern Illinois University School of Medicine
Springfield, Illinois 62702, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana 46202, United States
Riley Hospital for Children
Indianapolis, Indiana 46202, United States
Saint Vincent Hospital and Health Care Center
Indianapolis, Indiana 46260, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536, United States
Norton Children's Hospital
Louisville, Kentucky 40202, United States
Tulane University Health Sciences Center
New Orleans, Louisiana 70112, United States
Sinai Hospital of Baltimore
Baltimore, Maryland 21215, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287, United States
Walter Reed National Military Medical Center
Bethesda, Maryland 20889-5600, United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215, United States
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts 01655, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan 48201, United States
Michigan State University Clinical Center
East Lansing, Michigan 48824-7016, United States
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan 49503, United States
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan 49503, United States
Kalamazoo Center for Medical Studies
Kalamazoo, Michigan 49008, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota 55404, United States
Mayo Clinic
Rochester, Minnesota 55905, United States
University of Mississippi Medical Center
Jackson, Mississippi 39216, United States
University of Missouri - Ellis Fischel
Columbia, Missouri 65212, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri 64108, United States
Washington University School of Medicine
Saint Louis, Missouri 63110, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska 68114, United States
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada 89106, United States
Hackensack University Medical Center
Hackensack, New Jersey 07601, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey 08903, United States
Newark Beth Israel Medical Center
Newark, New Jersey 07112, United States
Saint Joseph's Regional Medical Center
Paterson, New Jersey 07503, United States
Overlook Hospital
Summit, New Jersey 07902, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico 87102, United States
Roswell Park Cancer Institute
Buffalo, New York 14263, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York 10032, United States
NYP/Weill Cornell Medical Center
New York, New York 10065, United States
State University of New York Upstate Medical University
Syracuse, New York 13210, United States
New York Medical College
Valhalla, New York 10595, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27599, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina 28203, United States
Sanford Broadway Medical Center
Fargo, North Dakota 58122, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio 44106, United States
Cleveland Clinic Foundation
Cleveland, Ohio 44195, United States
Nationwide Children's Hospital
Columbus, Ohio 43205, United States
Dayton Children's Hospital
Dayton, Ohio 45404, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio 43606, United States
Mercy Children's Hospital
Toledo, Ohio 43608, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104, United States
Legacy Emanuel Hospital and Health Center
Portland, Oregon 97227, United States
Oregon Health and Science University
Portland, Oregon 97239, United States
Geisinger Medical Center
Danville, Pennsylvania 17822, United States
Penn State Children's Hospital
Hershey, Pennsylvania 17033, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania 15224, United States
Rhode Island Hospital
Providence, Rhode Island 02903, United States

Showing the first 100 of 134 sites across 5 countries.

References and documents

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 33242441 ↗
Slayton 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 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 13, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00720109
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Jul 22, 2008
Start date: Jul 14, 2008
Primary completion: Dec 31, 2014
Completion: Mar 31, 2020
Results posted: Oct 7, 2016
Last update: Apr 13, 2020

Study contacts

William B Slayton

principal investigator · Children's Oncology Group

View the source record on ClinicalTrials.gov ↗

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