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Combination of Dasatinib and Peg-Interferon Alpha 2b in First Line for Chronic Myeloid Leukemia in Chronic Phase

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ClinicalTrials.gov Identifier: NCT01872442
Recruitment Status : Unknown
Verified June 2017 by Poitiers University Hospital.
Recruitment status was:  Active, not recruiting
First Posted : June 7, 2013
Last Update Posted : June 12, 2017
Sponsor:
Information provided by (Responsible Party):
Poitiers University Hospital

Brief Summary:
Interferon alpha was a therapy used in Chronic Myeloid Leukemia in Chronic phase prior to the advent of tyrosine kinase inhibitors. Synergistic effect of the combination of Peg-IFNα2a with Imatinib was demonstrated in the clinical SPIRIT trial. In this study, the investigators address the question of the efficacy and safety of dasatinib in combination with low dose of Peg-IFNα-2b as frontline therapy for patients with newly diagnosed Chronic Myeloid Leukemia in Chronic phase.

Condition or disease Intervention/treatment Phase
Chronic Phase of Chronic Myeloid Leukemia Drug: Dasatinib Drug: Peg-Interferon alpha2b Phase 2

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Study Type : Interventional  (Clinical Trial)
Study Start Date : October 2013
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: Dasatinib
Dasatinib,Bristol Myers Squibb
Drug: Dasatinib

Dasatinib 100mg daily starting at inclusion

If ANC ≤ 1.5.109/L, platelets ≤ 100.0.109/L or lymphocytes > 4.0.109/L at 3 months, dasatinib will be continued alone, and patients will be still followed in the study


Drug: Peg-Interferon alpha2b
30 µg weekly starting month 4- month 21

Experimental: Peg-Interferon alpha2b
Peg-Interferon alpha2b (Peg-IFN α2b), Merck
Drug: Dasatinib

Dasatinib 100mg daily starting at inclusion

If ANC ≤ 1.5.109/L, platelets ≤ 100.0.109/L or lymphocytes > 4.0.109/L at 3 months, dasatinib will be continued alone, and patients will be still followed in the study


Drug: Peg-Interferon alpha2b
30 µg weekly starting month 4- month 21




Primary Outcome Measures :
  1. Cumulative rate of molecular response [ Time Frame: at 12 months. ]

    Molecular response 4.5 (MR4.5) is defined by either a positive BCR-ABL/ABL ratio ≤ 0.0032 on the international scale or by undetectable BCR-ABL with the analysis of at least 32000 copies of ABL (according to the ELN recommendations by N. Cross et al., leukemia 2012).

    Centralized analyses of molecular response by RTQPCR will be performed for all molecular assessments in this study.



Secondary Outcome Measures :
  1. Rate of complete cytogenetic response [ Time Frame: 3, 6, 12, 18, 24 months, and every 12 months thereafter. ]
  2. Rate of major molecular responses [ Time Frame: 3, 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter. ]
  3. Rate of molecular response [ Time Frame: 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter. ]
    Rate of molecular response 4.5 and 5.0

  4. Kinetics and duration [ Time Frame: 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter ]
    Cumulative rate, Kinetics and duration CCR, MMR, MR4.5, MR5.0

  5. Rate of PegIFN-α2b and dasatinib discontinuation [ Time Frame: 24 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed Written Informed Consent.
  2. Target Population

    a)18 to 65 years b)Newly diagnosed (≤ 3 months) Philadelphia chromosome positive chronic CP-CML c)Major BCR-ABL transcripts d)Not previously treated for CML except with hydroxyurea or anagrelide e)ECOG Performance Status≤ 2 f)Adequate Organ Function. i)Total bilirubin< 2.0 times the institutional Upper Limit of Normal ii)Hepatic enzymes(AST, ALT )≤ 2.5 ULN iii)Serum Na, K+, Mg2+ and Ca2+ > Lower Limit of Normal (LLN) or supplemented iv)Serum Creatinine< 1.5 ULN g)Women of childbearing potential (WOCBP) must be using an adequate method of contraception.

  3. Free subject, without guardianship nor subordination,
  4. Health insurance coverage. -

Exclusion Criteria:

  1. Patients with BCR-ABL other than M-BCR-ABL, Philadelphia negative CML.
  2. Patients previously treated with Tyrosine Kinase Inhibitors (TKIs).
  3. Medical history and concurrent diseases :

    1. Hypersensitivity to any of the excipients of dasatinib
    2. Prior treatment with Interferon-α, contraindication to interferon-α, hypersensitivity to any of the excipients of PegIFNα2b,
    3. Concomitant immunosuppressive treatment or corticosteroids,
    4. Preexisting thyroid disease unless it is controlled with conventional treatment, Auto-immune thyroiditis,
    5. Autoimmune disorder, Chronic liver disease,
    6. Prior or ongoing severe psychiatric disease,
    7. Epilepsy or compromised central nervous system(CNS) function,
    8. HIV positivity, chronic hepatitis B or C,
    9. Uncontrolled or significant cardio vascular or pulmonary disease,

    i)Uncontrolled angina, myocardial infarction or congestive heart failure within 6 months, ii)Echocardiography with LVF < 45% or LLN, peak velocity of tricuspid regurgitant flow > 2,8 m/s iii)Pulmonary arterial hypertension (PAH), iv)Any history of clinically significant ventricular or supraventricular arrhythmias, v)Diagnosed congenital long QT syndrome, vi)Prolonged QTc interval > 450 msec (Fredericia) on 3 pre-entry electrocardiogram, vii)Subjects with hypokalemia or hypomagnesemia if it cannot be corrected, j)Other malignant disease during the last 5 years prior to the inclusion except basal cell carcinoma of the skin or carcinoma in situ of the cervix, k)History of significant bleeding disorder unrelated to CML, including: i)Diagnosed congenital bleeding disorders (e.g. von Willebrand's disease), ii)Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding. l)Another severe or life -threatening medical disease.

  4. Women who are pregnant or breastfeeding, WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after the last dose of study drug.
  5. Prohibited treatments and/or therapies:

    1. strong inhibitors of the CYP3A4,
    2. category I drugs that are generally accepted to have a risk of causing "Torsades de Pointes", Patients must discontinue the drug minimum 7 days prior to starting dasatinib.
  6. History /any condition for poor compliance to the treatment.
  7. Inability to freely provide consent through judiciary or administrative condition.
  8. Ongoing participation to another study.

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): NCT01872442


Sponsors and Collaborators
Poitiers University Hospital
Investigators
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Principal Investigator: Lydia ROY, MD Poitiers University Hospital

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Responsible Party: Poitiers University Hospital
ClinicalTrials.gov Identifier: NCT01872442     History of Changes
Other Study ID Numbers: DASA-PegIFN
First Posted: June 7, 2013    Key Record Dates
Last Update Posted: June 12, 2017
Last Verified: June 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Interferons
Interferon-alpha
Interferon alpha-2
Peginterferon alfa-2b
Dasatinib
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action