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

Primary Purpose

Leukemia

Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Nilotinib+mVPD
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia, untreated adult acute lymphoblastic leukemia

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Daegu Fatima Hospital
  • Kyungpook National University Hospital
  • Yeungnam University Medical Center
  • Daegu Catholic University Hospital
  • National Cancer Center - Korea
  • Chonnam National University Hwasun Hospital
  • Gyeongsang National University Hospital
  • Pusan National University Hospital
  • Inje University Seoul Paik Hospital
  • Seoul National University Hospital
  • Kyung Hee University Hospital
  • Samsung Medical Center
  • Asan Medical Center - University of Ulsan College of Medicine
  • Konkuk University Medical Center
  • Ajou University Hospital
  • Ulsan University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nilotinib+mVPD

Arm Description

Patients who were Philadelphia-positive, newly-diagnosed adult ALL and treated with nilotinib + mVPD treatment plan

Outcomes

Primary Outcome Measures

Proportion of Patients Achieving Hematologic and Molecular Complete Remission (CR) After Induction Therapy
approximate time: at the recovery of cytopenia

Secondary Outcome Measures

Disease(Relapse)-Free Survival
Overall Survival

Full Information

First Posted
February 13, 2009
Last Updated
August 7, 2015
Sponsor
Asan Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00844298
Brief Title
Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Official Title
Tasigna® (Nilotinib) Plus Multi-Agent Chemotherapy for Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia, untreated adult acute lymphoblastic leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
91 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nilotinib+mVPD
Arm Type
Experimental
Arm Description
Patients who were Philadelphia-positive, newly-diagnosed adult ALL and treated with nilotinib + mVPD treatment plan
Intervention Type
Drug
Intervention Name(s)
Nilotinib+mVPD
Other Intervention Name(s)
Mabthera, VCS, Daunobrastina, Solondo, Leunase, Cytarabine, Efosin, DBLMethotrexate
Intervention Description
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-) 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 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 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 Maintenance ◦Nilotinib 400mg bid/d (during 2 years, for patients without alloHCT) Consider alloHCT
Primary Outcome Measure Information:
Title
Proportion of Patients Achieving Hematologic and Molecular Complete Remission (CR) After Induction Therapy
Description
approximate time: at the recovery of cytopenia
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Disease(Relapse)-Free Survival
Time Frame
2 years
Title
Overall Survival
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kyoo H. Lee, MD
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Daegu Fatima Hospital
City
Daegu
ZIP/Postal Code
701-600
Country
Korea, Republic of
Facility Name
Kyungpook National University Hospital
City
Daegu
ZIP/Postal Code
702-701
Country
Korea, Republic of
Facility Name
Yeungnam University Medical Center
City
Daegu
ZIP/Postal Code
712-749
Country
Korea, Republic of
Facility Name
Daegu Catholic University Hospital
City
Daegu
Country
Korea, Republic of
Facility Name
National Cancer Center - Korea
City
Goyang
ZIP/Postal Code
410-769
Country
Korea, Republic of
Facility Name
Chonnam National University Hwasun Hospital
City
Jeollanam-do
ZIP/Postal Code
519-809
Country
Korea, Republic of
Facility Name
Gyeongsang National University Hospital
City
Jinju
ZIP/Postal Code
660-701
Country
Korea, Republic of
Facility Name
Pusan National University Hospital
City
Pusan
ZIP/Postal Code
602-739
Country
Korea, Republic of
Facility Name
Inje University Seoul Paik Hospital
City
Seoul
ZIP/Postal Code
100-032
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Kyung Hee University Hospital
City
Seoul
ZIP/Postal Code
130-702
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Asan Medical Center - University of Ulsan College of Medicine
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Facility Name
Konkuk University Medical Center
City
Seoul
ZIP/Postal Code
143-729
Country
Korea, Republic of
Facility Name
Ajou University Hospital
City
Suwon
ZIP/Postal Code
441-749
Country
Korea, Republic of
Facility Name
Ulsan University Hospital
City
Ulsan
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
26065651
Citation
Kim DY, Joo YD, Lim SN, Kim SD, Lee JH, Lee JH, Kim DH, Kim K, Jung CW, Kim I, Yoon SS, Park S, Ahn JS, Yang DH, Lee JJ, Lee HS, Kim YS, Mun YC, Kim H, Park JH, Moon JH, Sohn SK, Lee SM, Lee WS, Kim KH, Won JH, Hyun MS, Park J, Lee JH, Shin HJ, Chung JS, Lee H, Eom HS, Lee GW, Cho YU, Jang S, Park CJ, Chi HS, Lee KH; Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015 Aug 6;126(6):746-56. doi: 10.1182/blood-2015-03-636548. Epub 2015 Jun 11.
Results Reference
derived

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

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