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

This study is currently recruiting participants.
Verified April 2012 by Asan Medical Center
Sponsor:
Information provided by (Responsible Party):
Kyoo-Hyung Lee, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT00844298
First received: February 13, 2009
Last updated: April 18, 2012
Last verified: April 2012
History of Changes
  Purpose

RATIONALE: Nilotinib 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 nilotinib together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving nilotinib together with combination chemotherapy works in treating patients with newly diagnosed acute lymphoblastic leukemia.


Condition Intervention Phase
Leukemia
 Drug: Nilotinib+mVPD
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Tasigna® (Nilotinib) Plus Multi-Agent Chemotherapy for Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Proportion of patients achieving hematologic and molecular complete remission (CR) after induction therapy [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    approximate time: at the recovery of cytopenia


Secondary Outcome Measures:
  • Disease(relapse)-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: January 2009
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nilotinib+mVPD
Patients who were Philadelphia-positive, newly-diagnosed adult ALL and treated with nilotinib + mVPD treatment plan
 Drug: Nilotinib+mVPD

  1. Induction:

    • Daunorubicin 90 mg/m2/day by continuous iv infusion (d1-3)
    • Vincristine 2 mg iv push (d1, 8, 15, 22)
    • Prednisolone 60 mg/m2/day po (d1-28)
    • Nilotinib 400mg bid/d (d8-)

  2. Consolidation A (cycle1)

    • Daunorubicin 45 mg/m2/day by continuous iv (d1, 2)
    • Vincristine 2 mg iv (d1, 8)
    • Prednisolone 60 mg/m2/day po (d1-14)
    • Nilotinib 400mg bid/d

  3. Consolidation B (cycles 2&4)

    • Cytarabine 2,000 mg/m2/day iv over 2 hours (d1-4)
    • Etoposide 150 mg/m2/day iv over 3 hours (d1-4)
    • Nilotinib 400mg bid/d

  4. Consolidation C (cycles 3&5)

    • Methotrexate 220 mg/m2 iv bolus, then 60mg/m2/h for 36 hours (d1-2, 15-16)
    • Leucovorin followed immediately by 50 mg/m2 iv every 6hrs for three doses,
    • Nilotinib 400mg bid/d

  5. Maintenance

    ◦Nilotinib 400mg bid/d (during 2 years, for patients without alloHCT)

  6. Consider alloHCT
Other Names:
  • Mabthera
  • VCS
  • Daunobrastina
  • Solondo
  • Leunase
  • Cytarabine
  • Efosin
  • DBLMethotrexate

Detailed Description:

OBJECTIVES:

Primary

  • To determine the clinical efficacy of nilotinib and combination chemotherapy, in terms of hematologic and molecular complete remission (CR) rates, in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia or acute mixed lineage leukemia.

Secondary

  • To establish the prognostic factors for patients treated with this regimen.
  • To determine the duration of CR in patients treated with this regimen.
  • To determine the duration of progression-free and overall survival of these patients.
  • To determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to age (15 to 64 years vs ≥ 65 years).

  • Induction therapy: Patients receive daunorubicin hydrochloride IV continuously over 24 hours on days 1-3, vincristine sulfate IV on days 1 and 8, and oral prednisolone on days 1-14. Patients undergo bone marrow examination on day 14. Patients in hematologic remission proceed to consolidation therapy. Patients with residual leukemic cells > 5% receive an additional dose of daunorubicin hydrochloride IV continuously over 24 hours on day 15 before proceeding to consolidation therapy.
  • Consolidation therapy: For course 1, patients receive daunorubicin hydrochloride IV continuously over 24 hours on days 1 and 2, vincristine sulfate IV on days 1 and 8, and oral prednisolone on days 1-14. For courses 2 and 4, patients receive cytarabine IV over 2 hours and etoposide IV over 3 hours on days 1-4. For courses 3 and 5, patients receive methotrexate IV continuously over 36 hours on days 1, 2, 15, and 16 and leucovorin calcium IV every 6 hours for 3 doses and then orally until blood methotrexate levels are in a safe range.

Patients also receive oral nilotinib twice daily beginning on day 8 of induction therapy and continuing until the completion of consolidation therapy.

After completion of consolidation therapy, patients with a hematopoietic stem cell donor proceed to allogeneic hematopoietic stem cell transplantation (HSCT). Patients who do not undergo HSCT continue to receive oral nilotinib twice daily for up to 2 years after completion of consolidation therapy.

After completion of study therapy, patients are followed periodically for up to 1 year.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Newly diagnosed acute lymphoblastic leukemia or acute mixed lineage leukemia

    • Positive for Bcr-Abl fusion transcript (Philadelphia chromosome-positive disease) by RT-PCR

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Total bilirubin < 2 mg/dL
  • SGOT < 3 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN (unless considered tumor-related)
  • Creatinine < 2.0 mg/dL ULN
  • Serum amylase and lipase ≤ 1.5 times ULN
  • Potassium, magnesium, and phosphorus normal (supplementation allowed)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No rare hereditary problems with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption
  • No known sensitivity to any of the study drugs
  • No severe medical condition that, in the opinion of the investigator, would preclude study participation

  • No impaired cardiac function, including any of the following:

    • LVEF < 45% or below the lower limit of normal by ECHO
    • Long QT syndrome or known family history of long QT syndrome
    • Clinically significant resting bradycardia (< 50 beats per minute)
    • QTc > 450 msec on baseline ECG (using the QTcF formula)
    • Myocardial infarction within the past 12 months

    • Other clinically significant heart disease, including any of the following:

      • Unstable angina
      • Congestive heart failure
      • Uncontrolled hypertension
      • Uncontrolled arrhythmias
  • No other primary malignant disease requiring systemic treatment
  • No acute or chronic liver, pancreatic, or severe renal disease
  • No other severe and/or life-threatening medical disease
  • No history of significant congenital or acquired bleeding disorder unrelated to cancer
  • No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
  • No history of non-compliance

PRIOR CONCURRENT THERAPY:

  • More than 30 days since prior investigational agents
  • No concurrent medications that have the potential to prolong the QTc interval
  • No concurrent strong CYP3A4 inhibitors
  • No concurrent therapeutic coumarin derivatives
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00844298

Locations
Korea, Republic of
Kyungpook National University Hospital Recruiting
Daegu, Korea, Republic of, 702-701
Contact: Contact Person     82-53-950-6091        
Yeungnam University Medical Center Recruiting
Daegu, Korea, Republic of, 712-749
Contact: Contact Person     82-53-810-2114        
Daegu Catholic University Hospital Recruiting
Daegu, Korea, Republic of
Contact: Contact Person     82-53-626-5301        
Daegu Fatima Hospital Recruiting
Daegu, Korea, Republic of, 701-600
Contact: Contact Person     82-53-952-4051        
National Cancer Center - Korea Recruiting
Goyang, Korea, Republic of, 410-769
Contact: Contact Person     82-031-920-0001        
Chonnam National University Hwasun Hospital Recruiting
Jeollanam-do, Korea, Republic of, 519-809
Contact: Contact Person     82-61-379-7642        
Gyeongsang National University Hospital Recruiting
Jinju, Korea, Republic of, 660-701
Contact: Contact Person     82-55-750-8000        
Pusan National University Hospital Recruiting
Pusan, Korea, Republic of, 602-739
Contact: Contact Person     82-51-254-0171        
Konkuk University Medical Center Recruiting
Seoul, Korea, Republic of, 143-729
Contact: Contact Person     82-2-2030-5114        
Asan Medical Center - University of Ulsan College of Medicine Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Kyoo H. Lee, MD     82-2-2224-3210     khlee2@amc.seoul.kr    
Inje University Seoul Paik Hospital Recruiting
Seoul, Korea, Republic of, 100-032
Contact: Kang, RN     82-2-3010-5930     kang@nate.com    
Kyung Hee University Hospital Recruiting
Seoul, Korea, Republic of, 130-702
Contact: Lee, RN     82-2-950-3313     cutelee@naver.com    
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 135-710
Contact: Contact Person     82-2-3410-0200        
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Contact Person     82-2-763-5110        
Ajou University Hospital Recruiting
Suwon, Korea, Republic of, 441-749
Contact: Baek, RN     82-2-3010-7289     bsh5932@naver.com    
Ulsan University Hospital Recruiting
Ulsan, Korea, Republic of
Contact: Contact Person     82-52-250-7000        
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Kyoo H. Lee, MD Asan Medical Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Kyoo-Hyung Lee, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT00844298     History of Changes
Other Study ID Numbers: CDR0000632225, AMC-UUCM-2008-0310, NOVARTIS-AMC-UUCM-2008-0310
Study First Received: February 13, 2009
Last Updated: April 18, 2012
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Asan Medical Center:
Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
 Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2013