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Nilotinib Combined by Chemotherapy for Myeloid Blastic Phase of Chronic Myeloid Leukemia or Bcr-abl Positive Acute Myeloid Leukemia

Phase 2
18 Years
65 Years
Open (Enrolling)
Chronic Myeloid Leukemia in Myeloid Blast Crisis, Untreated Adult Acute Myeloid Leukemia

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Trial Information

Nilotinib Combined by Chemotherapy for Myeloid Blastic Phase of Chronic Myeloid Leukemia or Bcr-abl Positive Acute Myeloid Leukemia

LYMPHOMA (PH+ ALL) The trials combining imatinib with high-dose chemotherapy were
successfully resulting in high response rate and longer survival and a role for
bridging therapy to allogeneic hematopoietic stem cell transplantation (alloHSCT) by
means of concurrent or alternating regimen in patients with Philadelphia-positive (Ph+)
acute lymphoblastic leukemia (ALL).(24-29) Current combination therapy of imatinib and
chemotherapy became standard therapy of Ph+ ALL and new 2nd generation TKIs are
investigating. These experiences may be translated into the treatment of CML BP.

recently published papers of randomized trials comparing standard dose daunorubicin (45
mg/m2 for 3 days) and high dose daunorubicin (90 mg/m2 for 3 days) demonstrated
improved CR rate and survival with high dose daunorubicin in younger (60 years or
younger) and older (over 60 years) patients, respectively.(30, 31) Therefore high-dose
daunorubicin can be applied safely and effectively to the treatment of CML BP.

PHASE (MBP) OR PHYLADELPHIA POSITIVE AML We will try 2nd generation TKI, nilotinib and
high-dose daunorubicin induction chemotherapy combination to find out the combination
therapy can improve response rate and survival in patients with CML MBP.

Inclusion Criteria:

- Patients with previously-untreated patients having bcr-abl gene rearrangement (or
t(9;22)) and 20% or more of myeloid blasts in bone marrow and/or blood, or converted
CML CP/AP to MBP after initial imatinib treatment.

- 15 years old or older, but 65 years or younger

- Adequate performance status (Karnofsky score of 50 or more)

- Adequate hepatic and renal function (AST, ALT, bilirubin and creatinine < 2.5 x upper
normal limit). Elevation of AST or ALT due to hepatic infiltration of leukemic cells
will be permitted.

- Adequate cardiac function (left ventricular ejection fraction of 45% or more on heart
scan or echocardiogram)

- Signed and dated informed consent must be obtained.

Exclusion Criteria:

- Patients without bcr-abl gene rearrangement

- Acute lymphoblastic leukemia with bcr-abl gene rearrangement or t(9;22)

- Any previous history of TKIs except for imatinib in CML CP.

- Therapy-related leukemia or leukemia after myelodysplastic syndrome.

- Patients with CNS leukemia

- Patients with primary granulocytic sarcoma without bone marrow involvement

- Prior chemotherapy for leukemia or anthracycline treatment for any malignancy.
Hydroxyurea for reduction of leukemic cell burden before induction chemotherapy will
be permitted.

- Presence of significant active infection

- Presence of uncontrolled bleeding

- Significant cardiovascular disease including myocardial infarction within previous 6

- Cardiac dysfunction: LVEF < 45% or institutional lower normal range (any higher value
of them) by echocardiogram or MUGA scan; Long QT syndrome or its family history;
Clinically significant resting bradycardia (<50 beats/minute); QTc > 450 msec (by
QTcF formula) on baseline ECG . If QTcF > 450 msec and electrolytes are abnormal,
retest QTc after the correction of electrolytes; Myocardial infarction within 12
months; Other clinically significant cardiac diseases (for example, unstable angina,
congestive heart failure, uncontrolled hypertension or uncontrolled arrhythmia)

- Chronic or acute hepatic disease, pancreatic disease or severe renal disease

- Severe or life-threatening other medical conditions

- Any coexisting major illness or organ failure

- Patients with psychiatric disorder or mental deficiency severe as to make compliance
with the treatment unlike, and making informed consent impossible History of
congenital or acquired coagulopathy unrelated to malignancy

- Pregnancy issues: (a) pregnant woman, (b) lactating woman, (c) reproductive woman who
does not confirm negative baseline pregnancy test (d) man or reproductive woman who
cannot continue an appropriate contraceptive method (postmenopausal woman who has no
menstruation for last 12 months is considered as non-reproductive)

- Patients with a diagnosis of prior malignancy unless disease-free for at least 5
years following therapy with curative intent (except curatively treated nonmelanoma
skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)

- History of non-compliance or patient who cannot sign informed consent

- Hypersensitivity to nilotinib or any of the experience

- Concurrent medications (Gastrointestinal dysfunction that can significantly change
the absorption of test drug; - Strong CYP3A4 inhibitor and cannot stop or change the
medication before starting study; Medication to prolong QT interval and cannot stop
or change the medication before starting study) • The capsules contain lactose, and
nilotinib is therefore not recommended for patients with rare hereditary problems of
galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption

Type of Study:


Study Design:

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

Outcome Measure:

Complete remission rate

Outcome Description:

Primary purpose of this study is to define the efficacy of combined chemotherapy and nilotinib in chronic myeloid leukemia (CML) myeloid blastic phase (MBP) and bcr-abl positive acute myeloid leukemia (AML). The efficacy will be evaluated by complete remission (CR) rate.

Outcome Time Frame:

Within 8 weeks after induction therapy

Safety Issue:


Principal Investigator

Hawk Kim, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ulsan University Hospital, University of Ulsan College of Medicine


Korea: Food and Drug Administration

Study ID:




Start Date:

September 2012

Completion Date:

December 2017

Related Keywords:

  • Chronic Myeloid Leukemia in Myeloid Blast Crisis
  • Untreated Adult Acute Myeloid Leukemia
  • chronic myeloid leukemia
  • myeloid blastic phase
  • bcr-abl(+) acute myeloid leukemia
  • nilotinib
  • Blast Crisis
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive