Nilotinib-Chemotherapy in CML Myeloid BP or Bcr-abl(+) AML

NCT01690065 | Unknown Phase 2

• 1 other identifier: CAMN107AKR07T
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

Brief Summary

The current standard therapy in previously untreated adults with chronic phase (CP) of CML is imatinib and the result of long-term follow-up of IRIS study proves that imatinib for CML CP is reasonable therapy.(1, 2) However, some patients were initially diagnosed as advanced CML, accelerated phase (AP) or blastic phase (BP). Various chemotherapies were tried and were found that there were no highly effective chemotherapies for CML BP.(3-11) Imatinib in patients with these advanced CML is also disappointing because of low response rates as well as short response duration, and sudden transformation to BC is found even in initial CML CP patients. (12-17). Recent studies showed that nilotinib or dasatinib is better than imatinib in terms of rapid response and higher molecular response in newly diagnosed CML patients.(18-21) More potent bcr-abl suppression of nilotinib is supposed to be more active than imatinib even in patients with advanced CML. However, nilotinib in patients with imatinib-resistant or -intolerant CML BP showed low hematologic response and major cytogenetic response.(22, 23)

Conditions

Chronic Myeloid Leukemia in Myeloid Blast Crisis; Untreated Adult Acute Myeloid Leukemia

Keywords

chronic myeloid leukemia; myeloid blastic phase; bcr-abl(+) acute myeloid leukemia; nilotinib

Outcome Measures

Primary Outcomes (1)

• Complete remission rate

  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.

  Within 8 weeks after induction therapy

Secondary Outcomes (2)

• Safety

  Within 8 weeks after induction therapy

• Time-dependent variables

  at least 2 years

Study Arms (1)

Nilotinib+AD induction

EXPERIMENTAL

Nilotinib plus AD induction chemotherapy * AD regimen : Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 7 days (D 1-7) plus Daunorubicin 90 mg/m2/day iv daily for 3 days (D 1-3) * Nilotinib 400mg bid PO (continuous without interruption from D8 of induction chemotherapy) * Re-induction chemotherapy AD regimen : Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 5 days (D 1-5) plus Daunorubicin 45 mg/m2/day iv daily for 2 days (D 1-2)

Drug: Nilotinib+AD induction

Interventions

Nilotinib+AD induction DRUG

• Post-remission consolidation chemotherapy * 4 courses of high-dose cytarabine will be given as post-remission therapy. Cytarabine 3 g/m2 will be administered in a 3-hour iv infusion every 12 hours on days 1, 3, and 5 (a total of six doses per course). * Nilotinib 400mg bid PO will be administered continuously during consolidation chemotherapy and for 2 years after the consolidation therapy or until allogeneic hematopoietic stem cell transplantation

Also known as: Tasigna

Nilotinib+AD induction

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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 months
• 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

Sponsors & Collaborators

• Ulsan University Hospital: lead
• The Korean Society of Hematology CML working party: collaborator

Study Sites (2)

Seoul St Mary's Hospital

Seoul, South Korea

RECRUITING

Ulsan University Hospital

Ulsan, 682714, South Korea

RECRUITING

Related Publications (32)

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MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Hawk Kim, M.D., Ph.D.

  Ulsan University Hospital, University of Ulsan College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

+82-52-250-8892; kimhawkmd@gmail.com

Min Jung Kim, R.N.

CONTACT

+82-52-250-8515; enael@nate.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 11, 2012
• First Posted: September 21, 2012
• Study Start: September 1, 2012
• Primary Completion: September 1, 2019
• Study Completion: December 1, 2019
• Last Updated: May 11, 2016

Record last verified: 2016-05

Locations

KR (2)