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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Asan Medical Center.
Recruitment status was  Recruiting
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
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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      
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      
Yeungnam University Medical Center Recruiting
Daegu, Korea, Republic of, 712-749
Contact: Contact Person    82-53-810-2114      
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      
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Contact Person    82-2-763-5110      
Kyung Hee University Hospital Recruiting
Seoul, Korea, Republic of, 130-702
Contact: Lee, RN    82-2-950-3313    cutelee@naver.com   
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   
Konkuk University Medical Center Recruiting
Seoul, Korea, Republic of, 143-729
Contact: Contact Person    82-2-2030-5114      
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 135-710
Contact: Contact Person    82-2-3410-0200      
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:
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:
Abnormal Karyotype
Leukemia
Leukemia, Lymphoid
Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Chromosome Aberrations
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Translocation, Genetic

ClinicalTrials.gov processed this record on October 21, 2014