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

January 20, 2019 updated by: Hamad Medical Corporation

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

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Qatar
      • Doha, Qatar, 3050
        • National Center for Cancer Care & Research (NCCCR)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Sprycel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
12 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
12 months to 5 years
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)
5 years
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).
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hamad Medical Corporation

Investigators

  • Principal Investigator: Mohamed A Yassin, Hamad Medical Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 3, 2017

Primary Completion (Actual)

September 23, 2018

Study Completion (Actual)

September 23, 2018

Study Registration Dates

First Submitted

March 8, 2017

First Submitted That Met QC Criteria

March 8, 2017

First Posted (Actual)

March 14, 2017

Study Record Updates

Last Update Posted (Actual)

January 23, 2019

Last Update Submitted That Met QC Criteria

January 20, 2019

Last Verified

November 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17095/17

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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