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

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."
Brief Title
CMR Rate of Newly Diagnosed CML-CP Patients Treated With Nilotinib
Completion Date
Completion Date Type
Actual
Conditions
Chronic Myelogenous Leukemia in Chronic Phase
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.
Inclusion 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.

Gender
All
Gender Based
false
Keywords
CML
Chronic Myelogenous Leukemia
Leukemia
CML-CP
Nilotinib
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01227577
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CAMN107AUS28
Overall Status
Completed
Phases
Phase 4
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome 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.
Outcome Measure
Number of Participants With Confirmed Complete Molecular Response (CMR)
Outcome Time Frame
4 years
Secondary Outcomes
Outcome 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.
Outcome Time Frame
4 years
Outcome Measure
Number of Participants With Complete Cytogenetic Response (CCyR) and Major Molecular Response (MMR)
Outcome 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.
Outcome Time Frame
4 years
Outcome Measure
Time to CMR, CCyR and MMR
Outcome 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.
Outcome Time Frame
4 years
Outcome Measure
Duration of CMR, CCyR and MMR
Outcome Description
Progression to AP/BC is defined as loss of CCyR, MMR, and CMR and was summarized by frequencies and percentages.
Outcome Time Frame
4 years
Outcome Measure
Number of Participants With Progression to Accelerated Phase/Blastic Crisis (AP/BC)
Outcome 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.
Outcome Time Frame
4 years
Outcome Measure
Time to Progression of AP/BC
Outcome 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.
Outcome Time Frame
4 years
Outcome Measure
Number of Participants With Loss of CCyR, MMR and CMR
Outcome 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.
Outcome Time Frame
4 years
Outcome Measure
Number of Participants With CMR Who Were Dosed to 400 mg b.i.d.
Outcome 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.
Outcome Time Frame
4 years
Outcome Measure
Event-free Survival, Progression-free Survival and Overall Survival
Start Date
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Olga Derman
Investigator Email
ODERMAN@montefiore.org
Investigator Phone