Dasatinib Versus Nilotinib for Treatment Naïve Chronic Myeloid Leukemia

Study Overview
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Brief Summary
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DANIN study is a randomized, phase 3 clinical trial comparing 'head to head' Nilotinib versus Dasatinib as upfront therapy for patient with chronic myeloid leukemia. The efficacy of both drugs will be tested by measuring BCR/ABL (BCR-ABL = fusion gene from BCR (breakpoint cluster region gene/BCR gene product) and ABL (Abelson proto-oncogene)) using European Leukemia net recommendations the study will be conducted in NCCCR (National Center for Cancer Care & Research) sample size calculations detailed in the statistic part the clinical hematologist will recruit the patients this will include consenting process inclusion and exclusion criteria the molecular pathologist will do the molecular testing the clinical research coordinator and fellows will do the CRF (Case Report Form) as well as quality of life questionnaire and applying the protocol for evaluation of cardiac evaluation Molecular monitoring of BCR-ABL1 transcripts to assess treatment response in CML (Chronic Myeloid Leukemia).

Official Title
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Dasatinib Versus Nilotinib as Upfront Therapy for Treatment Naïve Chronic Myeloid Leukemia Chronic Phase

Conditions
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Chronic Myeloid Leukemia - Chronic Phase

Intervention / Treatment
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* Drug: Dasatinib 100 MG [Sprycel]
* Drug: Nilotinib 150mg oral capsule [Tasigna]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients 18 years or over. Patients must have all of the following: be enrolled within 3 months of initial diagnosis of CML-CP (Chronic Phase) (date of initial diagnosis is the date of first cytogenetic analysis) cytogenetic confirmation of the Philadelphia chromosome or variants of (9;22) translocations patients may have secondary chromosomal abnormalities in addition to the Philadelphia chromosome. < 15% blasts in peripheral blood and bone marrow; < 30% blasts plus promyelocytes in peripheral blood and bone marrow; < 20% basophils in peripheral blood, 100 x 109/L platelets or greater no evidence of extramedullary leukaemic involvement, with the exception of the hepatosplenomegaly. Written voluntary informed consent. Exclusion Criteria: 1 - Patients with Ph-negative, BCR-ABL-positive, disease are NOT eligible for the study. 2. Any prior treatment for CML with: any tyrosine kinase inhibitor (eg imatinib, dasatinib); busulphan; interferon-alpha; homoharringtonine; cytosine arabinoside; any other investigational agents (hydroxycarbamide and anagrelide are the only drugs permitted). Patients will be ineligible for the study if they have received any prior therapy with interferon-alpha or imatinib. No exceptions. 3. Patients who received prior chemotherapy, including regimens used in peripheral blood progenitor cells (PBPCs) mobilisation for haematopoietic progenitor-cell transplantation. (It is allowable to collect unmobilised PBPCs at diagnosis.) 4. Patient who have had any form of prior haemopoietic stem cell transplant, either autograft or allograft. 5. Patients with an ECOG (Eastern Cooperative Oncology Group) Performance Status Score of 2 or less. 6. Patients with serum bilirubin, AST (aspartate aminotransferase), ALT (alanine aminotransferase), or creatinine concentrations > 2.0 x the institutional upper limit of the normal range (IULN). 7. Patients with International normalized ratio (INR) or partial thromboplastin time (PTT) > 1.5 x IULN, with the exception of patients on treatment with oral anticoagulants. 8. Patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders, infection, angina, or Grade 3/4 cardiac problems as defined by the New York Heart Association Criteria. 9. Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required. 10. Patients who have undergone major surgery within 4 weeks of Study Day 1, or who have not recovered from prior major surgery. 11. Patients who are: pregnant, breast feeding, of childbearing potential without a negative pregnancy test prior to Study Day 1, and male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial (postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential). 12. Patients with a history of another malignancy either currently or within the past five years, with the exception of basal cell skin carcinoma or cervical carcinoma in situ. 13. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dasatinib<br>Dasatinib 100mg, once daily (QD), will be given to 25 patients, orally | Drug: Nilotinib 150mg oral capsule [Tasigna]<br>* Nilotinib (Tasigna) 300 milligram, twice-daily (BID) will be given to 25 patients orally<br>* Other names: Tasigna;|
| Experimental: Nilotinib<br>Nilotinib 300mg, twice daily (BID), will be given to 25 patients, orally | Drug: Dasatinib 100 MG [Sprycel]<br>* Dasatinib (Sprycel) 100 milligram, once-daily (QD) will be given to 25 patients orally<br>* Other names: Sprycel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with a Molecular Response Rate (MMR) at 12 Months from the baseline | Rate of MMR is defined as <= 0.1% BCR-ABL/ABL ratio by international scale (IS), measured by real-time quantitative polymerase chain reaction (RQ-PCR) which corresponds to a ≥ 3 log reduction of BCR-ABL transcript from standardized baseline. BCR-ABL = fusion gene from BCR (breakpoint cluster region gene/BCR gene product) and ABL (Abelson proto-oncogene) | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with a Durable Molecular Response Rate (MMR) from the baseline | Rate of MMR is defined as <= 0.1% BCR-ABL/ABL ratio by international scale (IS), measured by real-time quantitative polymerase chain reaction (RQ-PCR) which corresponds to a ≥ 3 log reduction of BCR-ABL transcript from standardized baseline. BCR-ABL = fusion gene from BCR (breakpoint cluster region gene/BCR gene product) and ABL (Abelson proto-oncogene) Number of patients with a maintained MMR for 5 years | 12 months to 5 years | 
| Number of patients with a Reduction in BCR-ABL Transcript Levels in both arms from the baseline | BCR-ABL ≤ 10% at 3 months BCR-ABL < 1% at 6 months BCR-ABL ≤ 0.1% at 12 months then MMR or better BCR-ABL = fusion gene from BCR (breakpoint cluster region gene/BCR gene product) and ABL (Abelson proto-oncogene) | 5 years | 
| Number of patients with a Complete Cytogenetic Response (CCyR) in both arms from the baseline | Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR (Complete Cytogenetic Response). | 5 years |