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

Primary Purpose

Chronic Myeloid Leukemia - Chronic Phase

Status

Terminated

Phase

Phase 3

Locations

Qatar

Study Type

Interventional

Intervention

Dasatinib 100 MG [Sprycel]

Nilotinib 150mg oral capsule [Tasigna]

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia - Chronic Phase

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

National Center for Cancer Care & Research (NCCCR)

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Dasatinib

Nilotinib

Arm Description

Dasatinib 100mg, once daily (QD), will be given to 25 patients, orally

Nilotinib 300mg, twice daily (BID), will be given to 25 patients, orally

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Number of patients with a Durable Molecular Response Rate (MMR) from the baseline

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)

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).

Full Information

NCT ID

NCT03079505

First Posted

March 8, 2017

Last Updated

January 20, 2019

Sponsor

Hamad Medical Corporation

1. Study Identification

Unique Protocol Identification Number

NCT03079505

Brief Title

Dasatinib Versus Nilotinib for Treatment Naïve Chronic Myeloid Leukemia

Acronym

DANIN

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Terminated

Why Stopped

Protocol Deviation

Study Start Date

August 3, 2017 (Actual)

Primary Completion Date

September 23, 2018 (Actual)

Study Completion Date

September 23, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hamad Medical Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Myeloid Leukemia - Chronic Phase

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dasatinib

Arm Type

Active Comparator

Arm Description

Dasatinib 100mg, once daily (QD), will be given to 25 patients, orally

Arm Title

Nilotinib

Arm Type

Experimental

Arm Description

Nilotinib 300mg, twice daily (BID), will be given to 25 patients, orally

Intervention Type

Drug

Intervention Name(s)

Dasatinib 100 MG [Sprycel]

Other Intervention Name(s)

Sprycel

Intervention Description

Dasatinib (Sprycel) 100 milligram, once-daily (QD) will be given to 25 patients orally

Intervention Type

Drug

Intervention Name(s)

Nilotinib 150mg oral capsule [Tasigna]

Other Intervention Name(s)

Tasigna

Intervention Description

Nilotinib (Tasigna) 300 milligram, twice-daily (BID) will be given to 25 patients orally

Primary Outcome Measure Information:

Title

Number of patients with a Molecular Response Rate (MMR) at 12 Months from the baseline

Description

Time Frame

12 Months

Secondary Outcome Measure Information:

Title

Number of patients with a Durable Molecular Response Rate (MMR) from the baseline

Description

Time Frame

12 months to 5 years

Title

Number of patients with a Reduction in BCR-ABL Transcript Levels in both arms from the baseline

Description

Time Frame

5 years

Title

Number of patients with a Complete Cytogenetic Response (CCyR) in both arms from the baseline

Description

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mohamed A Yassin

Organizational Affiliation

Hamad Medical Corporation

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Center for Cancer Care & Research (NCCCR)

City

Doha

ZIP/Postal Code

3050

Country

Qatar

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

11287980

Citation

Goldman JM, Melo JV. Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001 Apr 5;344(14):1084-6. doi: 10.1056/NEJM200104053441409. No abstract available.

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Dasatinib Versus Nilotinib for Treatment Naïve Chronic Myeloid Leukemia

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