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CMR Rate of Newly Diagnosed CML-CP Patients Treated With Nilotinib (MACS1428)

Primary Purpose

Chronic Myelogenous Leukemia in Chronic Phase

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Nilotinib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myelogenous Leukemia in Chronic Phase focused on measuring CML, Chronic Myelogenous Leukemia, Leukemia, CML-CP, Nilotinib

Eligibility Criteria

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

Inclusion Criteria:

Patients with Ph+ CML-CP within 3 months of diagnosis. Male or female patients' ≥ 18 years of age. Patients must have adequate end organ function.

Exclusion Criteria:

Previously documented T315I mutation. Other CML treatment is an exclusion criteria with the following exception: While awaiting study start, patients may be treated with anagrelide (no treatment duration limit), hydroxyurea (no treatment duration limit), and/or up to a 14 day supply of a tyrosine kinase inhibitor (TKI) approved by the FDA for frontline treatment. Patients taking a TKI prior to study entry must have at least a one day washout from their last dose of medication and have recovered from any side effects of such therapy.

Impaired cardiac function as defined by the protocol. Patients with contraindications to receiving nilotinib, including concomitant medications.

Sites / Locations

  • Pacific Cancer Medical Center, Inc.
  • Providence St. Joseph Medical Center Roy&Patricia Disney Fam Cancer
  • Bay Area Cancer Research Dept.ofBayAreaCancerResearch
  • St. Jude Heritage Medical Group Virginia Crosson Cancer Center
  • Sarah Cannon Research Institute SCRI
  • Advanced Medical Specialties
  • Pasco Hernando Oncology
  • Georgia Regents University MedCollege of GA Cancer Ctr 2
  • Stroger Cook County Hospital Division of Hematology & Onc
  • Louis A. Weiss Memorial Hospital
  • Indiana Blood and Marrow Institute
  • Cancer Center of Kansas
  • LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center(3)
  • University of Maryland
  • Dana Farber Cancer Institute
  • Henry Ford Hospital
  • St. Louis University Cancer Center
  • University of Nebraska Medical Center University of Nebraska Med Ctr
  • Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.
  • Montefiore Medical Center
  • University of Rochester Medical Ct James P Wilmot Cancer Ctr
  • Duke University Medical Center Duke University Med Ctr
  • Oregon Health & Science University
  • Cancer Centers of the Carolinas Cancer Center
  • Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
  • The Jones Clinic
  • Tennessee Oncology Sarah Cannon Research Inst.
  • Baylor Research Institute Baylor Research Institute (17)
  • Oncology Consultants Oncology Consultants, P.A.
  • Millennium Oncology
  • University of Virginia
  • Providence Regional Cancer Partnership

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nilotinib

Arm Description

Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.

Outcomes

Primary Outcome Measures

Number of Participants With Confirmed Complete Molecular Response (CMR)
CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl <=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.

Secondary Outcome Measures

Number of Participants With Complete Cytogenetic Response (CCyR) and Major Molecular Response (MMR)
CCyR was defined as 0% Philadelphia chromosome-positive (Ph+) metaphases in the bone marrow. MMR was defined as a 3 log reduction of Bcr-Abl transcripts from the standardized baseline on the international scale (equivalent to Bcr-Abl ≤ 0.1% IS). Bcr-Abl transcripts assessed by peripheral blood quatitative real time polymerase chain reaction (RQ-PCR) were used for the determination of all molecular responses.
Time to CMR, CCyR and MMR
Time to CMR, CCyR, and MMR was defined as the time from the date of enrollment to the date of first documented CMR, CCyR and MMR, respectively.
Duration of CMR, CCyR and MMR
Duration of CMR, CCyR and MMR were defined as the time from the first date of achievement of the response to the date of first documented loss of the response.
Number of Participants With Progression to Accelerated Phase/Blastic Crisis (AP/BC)
Progression to AP/BC is defined as loss of CCyR, MMR, and CMR and was summarized by frequencies and percentages.
Time to Progression of AP/BC
Time to progression of AP/BC was defined as the time from the date of the first dose of study drug to the date of first documented progression of AP/BC.
Number of Participants With Loss of CCyR, MMR and CMR
Rate of loss of CMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.0032% IS. Rate of loss of CCyR was defined as an increase in the Ph+ bone marrow cells to greater than 0%. Rate of loss of MMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.1% IS.
Number of Participants With CMR Who Were Dosed to 400 mg b.i.d.
CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl <=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.
Event-free Survival, Progression-free Survival and Overall Survival
Event-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: loss of Complete Hematological Response (CHR), loss of CCyR, loss of Partial Cytogenetic Response (PCyR), progression to the accelerated phase or blast crisis, and death from any cause. Progression-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: progression to the accelerated phase or blast crisis, death, and loss of CMR. Overall survival was defined as the time from the date of enrollment until death due to any cause.

Full Information

First Posted
October 21, 2010
Last Updated
January 11, 2016
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01227577
Brief Title
CMR Rate of Newly Diagnosed CML-CP Patients Treated With Nilotinib
Acronym
MACS1428
Official Title
A Single-arm, Open-label, Multi-center Study of Complete Molecular Response (CMR) in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
"This is a single-arm, open-label, multi-center study of complete molecular response (CMR) in adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP). The study is designed to evaluate early and deep molecular responses up to 4 years on nilotinib treatment. The primary end point is Rate of confirmed CMR in newly diagnosed Philadelphia chromosome positive CML-CP patients."

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myelogenous Leukemia in Chronic Phase
Keywords
CML, Chronic Myelogenous Leukemia, Leukemia, CML-CP, Nilotinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
128 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nilotinib
Arm Type
Experimental
Arm Description
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Intervention Type
Drug
Intervention Name(s)
Nilotinib
Intervention Description
Nilotinib was supplied as 150 mg and 200 mg hard gelatin capsules.
Primary Outcome Measure Information:
Title
Number of Participants With Confirmed Complete Molecular Response (CMR)
Description
CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl <=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Number of Participants With Complete Cytogenetic Response (CCyR) and Major Molecular Response (MMR)
Description
CCyR was defined as 0% Philadelphia chromosome-positive (Ph+) metaphases in the bone marrow. MMR was defined as a 3 log reduction of Bcr-Abl transcripts from the standardized baseline on the international scale (equivalent to Bcr-Abl ≤ 0.1% IS). Bcr-Abl transcripts assessed by peripheral blood quatitative real time polymerase chain reaction (RQ-PCR) were used for the determination of all molecular responses.
Time Frame
4 years
Title
Time to CMR, CCyR and MMR
Description
Time to CMR, CCyR, and MMR was defined as the time from the date of enrollment to the date of first documented CMR, CCyR and MMR, respectively.
Time Frame
4 years
Title
Duration of CMR, CCyR and MMR
Description
Duration of CMR, CCyR and MMR were defined as the time from the first date of achievement of the response to the date of first documented loss of the response.
Time Frame
4 years
Title
Number of Participants With Progression to Accelerated Phase/Blastic Crisis (AP/BC)
Description
Progression to AP/BC is defined as loss of CCyR, MMR, and CMR and was summarized by frequencies and percentages.
Time Frame
4 years
Title
Time to Progression of AP/BC
Description
Time to progression of AP/BC was defined as the time from the date of the first dose of study drug to the date of first documented progression of AP/BC.
Time Frame
4 years
Title
Number of Participants With Loss of CCyR, MMR and CMR
Description
Rate of loss of CMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.0032% IS. Rate of loss of CCyR was defined as an increase in the Ph+ bone marrow cells to greater than 0%. Rate of loss of MMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.1% IS.
Time Frame
4 years
Title
Number of Participants With CMR Who Were Dosed to 400 mg b.i.d.
Description
CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl <=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.
Time Frame
4 years
Title
Event-free Survival, Progression-free Survival and Overall Survival
Description
Event-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: loss of Complete Hematological Response (CHR), loss of CCyR, loss of Partial Cytogenetic Response (PCyR), progression to the accelerated phase or blast crisis, and death from any cause. Progression-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: progression to the accelerated phase or blast crisis, death, and loss of CMR. Overall survival was defined as the time from the date of enrollment until death due to any cause.
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with Ph+ CML-CP within 3 months of diagnosis. Male or female patients' ≥ 18 years of age. Patients must have adequate end organ function. Exclusion Criteria: Previously documented T315I mutation. Other CML treatment is an exclusion criteria with the following exception: While awaiting study start, patients may be treated with anagrelide (no treatment duration limit), hydroxyurea (no treatment duration limit), and/or up to a 14 day supply of a tyrosine kinase inhibitor (TKI) approved by the FDA for frontline treatment. Patients taking a TKI prior to study entry must have at least a one day washout from their last dose of medication and have recovered from any side effects of such therapy. Impaired cardiac function as defined by the protocol. Patients with contraindications to receiving nilotinib, including concomitant medications.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Pacific Cancer Medical Center, Inc.
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Providence St. Joseph Medical Center Roy&Patricia Disney Fam Cancer
City
Burbank
State/Province
California
ZIP/Postal Code
91505-6866
Country
United States
Facility Name
Bay Area Cancer Research Dept.ofBayAreaCancerResearch
City
Concord
State/Province
California
ZIP/Postal Code
94520
Country
United States
Facility Name
St. Jude Heritage Medical Group Virginia Crosson Cancer Center
City
Yorba Linda
State/Province
California
ZIP/Postal Code
92886
Country
United States
Facility Name
Sarah Cannon Research Institute SCRI
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Facility Name
Advanced Medical Specialties
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Pasco Hernando Oncology
City
New Port Richey
State/Province
Florida
ZIP/Postal Code
34652
Country
United States
Facility Name
Georgia Regents University MedCollege of GA Cancer Ctr 2
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Stroger Cook County Hospital Division of Hematology & Onc
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Louis A. Weiss Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60640
Country
United States
Facility Name
Indiana Blood and Marrow Institute
City
Beach Grove
State/Province
Indiana
ZIP/Postal Code
46107
Country
United States
Facility Name
Cancer Center of Kansas
City
Witchita
State/Province
Kansas
ZIP/Postal Code
67214-3728
Country
United States
Facility Name
LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center(3)
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70115
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
St. Louis University Cancer Center
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center University of Nebraska Med Ctr
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
University of Rochester Medical Ct James P Wilmot Cancer Ctr
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Duke University Medical Center Duke University Med Ctr
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201
Country
United States
Facility Name
Cancer Centers of the Carolinas Cancer Center
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
The Jones Clinic
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Tennessee Oncology Sarah Cannon Research Inst.
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Baylor Research Institute Baylor Research Institute (17)
City
Dallas
State/Province
Texas
ZIP/Postal Code
75204
Country
United States
Facility Name
Oncology Consultants Oncology Consultants, P.A.
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
Millennium Oncology
City
Houston
State/Province
Texas
ZIP/Postal Code
77090
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Providence Regional Cancer Partnership
City
Everett
State/Province
Washington
ZIP/Postal Code
98201
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30912699
Citation
Berdeja JG, Heinrich MC, Dakhil SR, Goldberg SL, Wadleigh M, Kuriakose P, Cortes J, Radich J, Helton B, Rizzieri D, Paley C, Dautaj I, Mauro MJ. Rates of deep molecular response by digital and conventional PCR with frontline nilotinib in newly diagnosed chronic myeloid leukemia: a landmark analysis. Leuk Lymphoma. 2019 Oct;60(10):2384-2393. doi: 10.1080/10428194.2019.1590569. Epub 2019 Mar 26.
Results Reference
derived

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CMR Rate of Newly Diagnosed CML-CP Patients Treated With Nilotinib

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