Dasatinib Versus Nilotinib for Treatment Naïve Chronic Myeloid Leukemia

NCT03079505 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: 17095/17
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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).

Conditions

Chronic Myeloid Leukemia - Chronic Phase

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

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

  12 months to 5 years

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

  5 years

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

  5 years

Study Arms (2)

Dasatinib

ACTIVE COMPARATOR

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

Drug: Nilotinib 150mg oral capsule [Tasigna]

Nilotinib

EXPERIMENTAL

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

Drug: Dasatinib 100 MG [Sprycel]

Interventions

Dasatinib 100 MG [Sprycel] DRUG

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

Also known as: Sprycel

Nilotinib

Nilotinib 150mg oral capsule [Tasigna] DRUG

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

Also known as: Tasigna

Dasatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• x 109/L platelets or greater
• no evidence of extramedullary leukaemic involvement, with the exception of the hepatosplenomegaly.
• Written voluntary informed consent.

You may not qualify if:

• Patients with Ph-negative, BCR-ABL-positive, disease are NOT eligible for the study.
• \. 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.
• \. 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.
• \. Patients with an ECOG (Eastern Cooperative Oncology Group) Performance Status Score of 2 or less.
• \. 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).
• \. 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.
• \. 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.
• \. Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required.
• \. Patients who have undergone major surgery within 4 weeks of Study Day 1, or who have not recovered from prior major surgery.
• \. 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).
• \. 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.

Sponsors & Collaborators

• Hamad Medical Corporation: lead

Study Sites (1)

National Center for Cancer Care & Research (NCCCR)

Doha, 3050, Qatar

Location

Related Publications (9)

• 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.

  PMID: 11287980 BACKGROUND

• Hehlmann R, Saussele S. Treatment of chronic myeloid leukemia in blast crisis. Haematologica. 2008 Dec;93(12):1765-9. doi: 10.3324/haematol.2008.001214. No abstract available.

  PMID: 19050065 BACKGROUND

• Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, Cervantes F, Hochhaus A, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, Larson RA; IRIS Investigators. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006 Dec 7;355(23):2408-17. doi: 10.1056/NEJMoa062867.

  PMID: 17151364 BACKGROUND

• 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.

  BACKGROUND

• de Lavallade H, Apperley JF, Khorashad JS, Milojkovic D, Reid AG, Bua M, Szydlo R, Olavarria E, Kaeda J, Goldman JM, Marin D. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol. 2008 Jul 10;26(20):3358-63. doi: 10.1200/JCO.2007.15.8154. Epub 2008 Jun 2.

  PMID: 18519952 BACKGROUND

• O'Hare T, Walters DK, Stoffregen EP, Jia T, Manley PW, Mestan J, Cowan-Jacob SW, Lee FY, Heinrich MC, Deininger MW, Druker BJ. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005 Jun 1;65(11):4500-5. doi: 10.1158/0008-5472.CAN-05-0259.

  PMID: 15930265 BACKGROUND

• Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DiPersio J, DeAngelo DJ, Abruzzese E, Rea D, Baccarani M, Muller MC, Gambacorti-Passerini C, Wong S, Lustgarten S, Rivera VM, Clackson T, Turner CD, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes T, Goldman JM, Shah NP, Kantarjian H; PACE Investigators. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013 Nov 7;369(19):1783-96. doi: 10.1056/NEJMoa1306494. Epub 2013 Nov 1.

  PMID: 24180494 BACKGROUND

• Cortes JE, Jones D, O'Brien S, Jabbour E, Ravandi F, Koller C, Borthakur G, Walker B, Zhao W, Shan J, Kantarjian H. Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. J Clin Oncol. 2010 Jan 20;28(3):398-404. doi: 10.1200/JCO.2009.25.4920. Epub 2009 Dec 14.

  PMID: 20008620 BACKGROUND

• Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, Moiraghi B, Shen Z, Mayer J, Pasquini R, Nakamae H, Huguet F, Boque C, Chuah C, Bleickardt E, Bradley-Garelik MB, Zhu C, Szatrowski T, Shapiro D, Baccarani M. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010 Jun 17;362(24):2260-70. doi: 10.1056/NEJMoa1002315. Epub 2010 Jun 5.

  PMID: 20525995 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase

Interventions

Dasatinib; nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Mohamed A Yassin

  Hamad Medical Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2017
• First Posted: March 14, 2017
• Study Start: August 3, 2017
• Primary Completion: September 23, 2018
• Study Completion: September 23, 2018
• Last Updated: January 23, 2019

Record last verified: 2018-11

Locations

QA (1)