Know Cancer

or
forgot password

Phase II Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy Plus Dasatinib (NSC #732517, IND #73969) and Continuation Therapy With Dasatinib Alone in Newly Diagnosed Patients With Core Binding Factor Acute Myeloid Leukemia (AML)


Phase 2
18 Years
N/A
Not Enrolling
Both
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Secondary Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia

Thank you

Trial Information

Phase II Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy Plus Dasatinib (NSC #732517, IND #73969) and Continuation Therapy With Dasatinib Alone in Newly Diagnosed Patients With Core Binding Factor Acute Myeloid Leukemia (AML)


PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of dasatinib with intensive induction therapy
(daunorubicin hydrochloride and cytarabine), consolidation chemotherapy (high-dose
cytarabine), and as single agent in maintenance therapy in patients with newly diagnosed
core-binding factor acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

I. To assess clinical outcomes such as event-free survival (EFS), complete response rate
(CR), cumulative incidence of relapse (CIR), cumulative incidence of death (CID),
disease-free survival (DFS), and overall survival (OS) of patients treated with these
regimens.

II. To describe the frequency and severity of adverse events of patients treated on this
study during induction, consolidation, and continuation therapy.

III. To describe the interaction of pretreatment disease and patient characteristics
including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood
cell count and hemogram, and performance status on clinical outcomes.

OUTLINE: This is a multicenter study.

INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride IV on days 1-3,
cytarabine IV continuously over 168 hours on days 1-7, and dasatinib orally (PO) once daily
on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and
patients with non-responsive disease on day 21 (bone marrow cellularity ≥ 20 % and leukemia
blasts ≥ 5%) receive a second course of induction therapy.

INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3,
cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO once a day on days
6-19. Patients achieving complete response receive consolidation therapy.

CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3,
and 5, and dasatinib PO once daily on days 6-26. Treatment repeats every 28 days for 4
courses in the absence of disease progression or unacceptable toxicity. Patients in complete
remission receive continuation therapy.

CONTINUATION THERAPY: Patients receive dasatinib PO on days 1-28. Treatment repeats every 28
days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 2 months for 2 years,
every 3 months for 2 years, and then every year for a up to 10 years.


Inclusion Criteria:



- Newly diagnosed acute myeloid leukemia (AML)

- Molecular diagnosis of core-binding factor (CBF) AML by RT-PCR positive for any
of the following:

- RUNX1-RUNX1T1 fusion transcript resulting from t(8;21)(q22;q22) or a
variant form

- CBFB-MYH11 fusion transcript resulting from inv(16)(p13.1q22)
ort(16;16)(p13.1;q22) (any % bone marrow or blood blasts render the
diagnosis of CBFAML based on the WHO classification)

- AML with a history of antecedent myelodysplasia (MDS) allowed

- Patients who have developed therapy-related myeloid neoplasm (t-MN) after prior
radiotherapy or chemotherapy for another cancer or disorder allowed

- Must be registered on CALGB-8461 and CALGB-20202 protocols

- May also be registered on CALGB-9665

- Bilirubin < 2.5 times upper limit of normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must agree to use two acceptable methods of birth control before,
during, and for ≥ 12 weeks after treatment is complete:

- One highly effective method (e.g., IUD, hormonal, tubal ligation, or partner's
vasectomy)

- One additional effective method (e.g., latex condom, diaphragm, or cervical cap)

- Left ventricular ejection fraction >= lower limit of institutional normal by MUGA or
ECHO scan

- No myocardial infarction within 6 months

- No ventricular tachyarrhythmia within 6 months

- No major conduction abnormality (unless a cardiac pacemaker is present)

- No patients with congenital QT syndrome or non-congenital QTc prolongation (≥ 480
msecs) that cannot be corrected by infusion of electrolytes and/or discontinuation of
other medications prior to start of treatment

- No concurrent proton pump inhibitors

- No prior chemotherapy for leukemia or myelodysplasia except the following:

- Emergency leukapheresis

- Emergency treatment for hyperleukocytosis with hydroxyurea

- Cranial radiotherapy for CNS leukostasis (one dose only)

- Growth factor and/or cytokine support and/or non-cytotoxic molecular-targeted
agents

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Survival rate during induction therapy

Outcome Time Frame:

30 days

Safety Issue:

No

Principal Investigator

Guido Marcucci

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02615

NCT ID:

NCT01238211

Start Date:

December 2010

Completion Date:

Related Keywords:

  • Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Secondary Acute Myeloid Leukemia
  • Untreated Adult Acute Myeloid Leukemia
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Roswell Park Cancer Institute Buffalo, New York  14263
University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
Washington University School of Medicine Saint Louis, Missouri  63110
Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114
Methodist Medical Center of Illinois Peoria, Illinois  61636
Dana-Farber Cancer Institute Boston, Massachusetts  02115
North Shore University Hospital Manhasset, New York  11030
Eastern Maine Medical Center Bangor, Maine  04401
Weill Medical College of Cornell University New York, New York  10021
Long Island Jewish Medical Center New Hyde Park, New York  11040
Munson Medical Center Traverse City, Michigan  49684
Brigham and Women's Hospital Boston, Massachusetts  02115
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Columbus, Ohio  43210-1240
Beebe Medical Center Lewes, Delaware  19958
Memorial Hospital Carthage, Illinois  62321
Mason District Hospital Havana, Illinois  62644
McDonough District Hospital Macomb, Illinois  61455
BroMenn Regional Medical Center Normal, Illinois  61761
Proctor Hospital Peoria, Illinois  61614
Perry Memorial Hospital Princeton, Illinois  61356
Mecosta County Medical Center Big Rapids, Michigan  49307
Mountainview Medical Berlin, Vermont  05602
Eureka Hospital Eureka, Illinois  61530
Graham Hospital Association Canton, Illinois  61520
Saint Joseph Medical Center Joliet, Illinois  60435
Harold Alfond Center for Cancer Care Augusta, Maine  04330
Union Hospital of Cecil County Elkton MD, Maryland  21921
Dartmouth Hitchcock Medical Center Lebanon, New Hampshire  03756
University Of Vermont Burlington,, Vermont  05403
Florida Hospital Orlando, Florida  32803
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
Wake Forest University Health Sciences Winston-Salem, North Carolina  27157
OSF Saint Francis Medical Center Peoria, Illinois  61637
Community Cancer Center Foundation Normal, Illinois  61761
Illinois CancerCare-Ottawa Clinic Ottawa, Illinois  61350
Ottawa Regional Hospital and Healthcare Center Ottawa, Illinois  61350
Pekin Cancer Treatment Center Pekin, Illinois  61554
Illinois Oncology Research Association CCOP Peoria, Illinois  61615
Illinois CancerCare-Peoria Peoria, Illinois  61615
Illinois Valley Hospital Peru, Illinois  61354
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard Fort Wayne, Indiana  46845
Grand Rapids Clinical Oncology Program Grand Rapids, Michigan  49503
Saint Mary's Health Care Grand Rapids, Michigan  49503
Spectrum Health at Butterworth Campus Grand Rapids, Michigan  49503
Mercy Health Partners-Mercy Campus Muskegon, Michigan  49443
Cooper Hospital University Medical Center Camden, New Jersey  08103
State University of New York Upstate Medical University Syracuse, New York  13210
Wayne Memorial Hospital Goldsboro, North Carolina  27534
University of Maryland Greenebaum Cancer Center Baltimore, Maryland  21201
University of Illinois Chicago, Illinois  60612
Illinois CancerCare-Bloomington Bloomington%, Illinois  61701
Illinois CancerCare-Canton Canton, Illinois  61520
Illinois CancerCare-Eureka Eureka, Illinois  61530
Illinois CancerCare-Macomb Macomb, Illinois  61455
Illinois CancerCare-Community Cancer Center Normal, Illinois  61761
Illinois CancerCare-Pekin Pekin, Illinois  61603
Illinois CancerCare-Peru Peru, Illinois  61354
Illinois CancerCare-Spring Valley Spring Valley, Illinois  61362
University of Missouri - Ellis Fischel Columbia, Missouri  65203
Monter Cancer Center Lake Success, New York  11042
Spectrum Health Reed City Hospital Reed City, Michigan  49677
North Shore-LIJ Health System CCOP Manhasset, New York  11030
Christiana Care Health System-Christiana Hospital Newark, Delaware  19718
Bronson Battle Creek Battle Creek, Michigan  49017