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Dasatinib Versus Nilotinib for Treatment Naïve Chronic Myeloid Leukemia (DANIN)

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ClinicalTrials.gov Identifier: NCT03079505
Recruitment Status : Terminated (Protocol Deviation)
First Posted : March 14, 2017
Last Update Posted : January 23, 2019
Sponsor:
Information provided by (Responsible Party):
Hamad Medical Corporation

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia - Chronic Phase Drug: Dasatinib 100 MG [Sprycel] Drug: Nilotinib 150mg oral capsule [Tasigna] Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dasatinib Versus Nilotinib as Upfront Therapy for Treatment Naïve Chronic Myeloid Leukemia Chronic Phase
Actual Study Start Date : August 3, 2017
Actual Primary Completion Date : September 23, 2018
Actual Study Completion Date : September 23, 2018


Arm Intervention/treatment
Active Comparator: Dasatinib
Dasatinib 100mg, once daily (QD), will be given to 25 patients, orally
Drug: Nilotinib 150mg oral capsule [Tasigna]
Nilotinib (Tasigna) 300 milligram, twice-daily (BID) will be given to 25 patients orally
Other Name: Tasigna

Experimental: Nilotinib
Nilotinib 300mg, twice daily (BID), will be given to 25 patients, orally
Drug: Dasatinib 100 MG [Sprycel]
Dasatinib (Sprycel) 100 milligram, once-daily (QD) will be given to 25 patients orally
Other Name: Sprycel




Primary Outcome Measures :
  1. Number of patients with a Molecular Response Rate (MMR) at 12 Months from the baseline [ Time Frame: 12 Months ]
    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)


Secondary Outcome Measures :
  1. Number of patients with a Durable Molecular Response Rate (MMR) from the baseline [ Time Frame: 12 months to 5 years ]
    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

  2. Number of patients with a Reduction in BCR-ABL Transcript Levels in both arms from the baseline [ Time Frame: 5 years ]

    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)


  3. Number of patients with a Complete Cytogenetic Response (CCyR) in both arms from the baseline [ Time Frame: 5 years ]
    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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients 18 years or over.
  2. 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.
  3. 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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03079505


Locations
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Qatar
National Center for Cancer Care & Research (NCCCR)
Doha, Qatar, 3050
Sponsors and Collaborators
Hamad Medical Corporation
Investigators
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Principal Investigator: Mohamed A Yassin Hamad Medical Corporation

Publications:
Deininger M, O'Brien SG, Guilhot F, et al. International randomized study of interferon vs STI571 (IRIS) 8-year follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with imatinib [abstract]. Blood (ASH Annual Meeting Abstracts) 2009;114(22). Abstract 1126.

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Responsible Party: Hamad Medical Corporation
ClinicalTrials.gov Identifier: NCT03079505     History of Changes
Other Study ID Numbers: 17095/17
First Posted: March 14, 2017    Key Record Dates
Last Update Posted: January 23, 2019
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action