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

August 7, 2015 updated by: Kyoo-Hyung Lee, Asan Medical Center

Tasigna® (Nilotinib) Plus Multi-Agent Chemotherapy for Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

91

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Daegu, Korea, Republic of
        • Daegu Catholic University Hospital
      • Daegu, Korea, Republic of, 701-600
        • Daegu Fatima Hospital
      • Daegu, Korea, Republic of, 702-701
        • Kyungpook National University Hospital
      • Daegu, Korea, Republic of, 712-749
        • Yeungnam University Medical Center
      • Goyang, Korea, Republic of, 410-769
        • National Cancer Center - Korea
      • Jeollanam-do, Korea, Republic of, 519-809
        • Chonnam National University Hwasun Hospital
      • Jinju, Korea, Republic of, 660-701
        • Gyeongsang National University Hospital
      • Pusan, Korea, Republic of, 602-739
        • Pusan National University Hospital
      • Seoul, Korea, Republic of, 135-710
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 110-744
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 143-729
        • Konkuk University Medical Center
      • Seoul, Korea, Republic of, 100-032
        • Inje University Seoul Paik Hospital
      • Seoul, Korea, Republic of, 130-702
        • Kyung Hee University Hospital
      • Seoul, Korea, Republic of, 138-736
        • Asan Medical Center - University of Ulsan College of Medicine
      • Suwon, Korea, Republic of, 441-749
        • Ajou University Hospital
      • Ulsan, Korea, Republic of
        • Ulsan University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • Cytarabine
  • Mabthera
  • Leunase
  • VCS
  • Daunobrastina
  • Solondo
  • Efosin
  • DBLMethotrexate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Patients Achieving Hematologic and Molecular Complete Remission (CR) After Induction Therapy
Time Frame: 1 month
approximate time: at the recovery of cytopenia
1 month

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival
Time Frame: 2 years
2 years
Disease(Relapse)-Free Survival
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (ACTUAL)

June 1, 2012

Study Completion (ACTUAL)

July 1, 2014

Study Registration Dates

First Submitted

February 13, 2009

First Submitted That Met QC Criteria

February 13, 2009

First Posted (ESTIMATE)

February 16, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

September 7, 2015

Last Update Submitted That Met QC Criteria

August 7, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000632225
  • AMC-UUCM-2008-0310
  • NOVARTIS-AMC-UUCM-2008-0310

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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