Trial record 1 of 1 for:    CAMN107AUS28
Previous Study | Return to List | Next Study

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01227577
First received: October 21, 2010
Last updated: January 11, 2016
Last verified: January 2016
  Purpose
"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."

Condition Intervention Phase
Chronic Myelogenous Leukemia in Chronic Phase
Drug: Nilotinib
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Participants With Confirmed Complete Molecular Response (CMR) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: 4 years ] [ Designated as safety issue: No ]

    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 Frame: 4 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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 Frame: 4 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 128
Study Start Date: November 2010
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nilotinib
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
Drug: Nilotinib
Nilotinib was supplied as 150 mg and 200 mg hard gelatin capsules.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  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: NCT01227577

  Show 32 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01227577     History of Changes
Other Study ID Numbers: CAMN107AUS28 
Study First Received: October 21, 2010
Results First Received: November 19, 2015
Last Updated: January 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
CML
Chronic Myelogenous Leukemia
Leukemia
CML-CP
Nilotinib

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on May 30, 2016