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

NCT01872442 | Completed Phase 2

• 1 other identifier: DASA-PegIFN
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Phase of Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Cumulative rate of molecular response

  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.

  at 12 months.

Secondary Outcomes (5)

• Rate of complete cytogenetic response

  3, 6, 12, 18, 24 months, and every 12 months thereafter.

• Rate of major molecular responses

  3, 6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter.

• Rate of molecular response

  6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter.

• Kinetics and duration

  6, 9, 12, 15, 18, 21, 24 months and every 6 months thereafter

• Rate of PegIFN-α2b and dasatinib discontinuation

  24 months

Study Arms (2)

Dasatinib

EXPERIMENTAL

Dasatinib,Bristol Myers Squibb

Drug: Dasatinib; Drug: Peg-Interferon alpha2b

Peg-Interferon alpha2b

EXPERIMENTAL

Peg-Interferon alpha2b (Peg-IFN α2b), Merck

Drug: Dasatinib; Drug: Peg-Interferon alpha2b

Interventions

Dasatinib DRUG

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

Dasatinib; Peg-Interferon alpha2b

Peg-Interferon alpha2b DRUG

30 µg weekly starting month 4- month 21

Dasatinib; Peg-Interferon alpha2b

Eligibility Criteria

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

You may qualify if:

• Signed Written Informed Consent.
• 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.
• Free subject, without guardianship nor subordination,
• Health insurance coverage. -

You may not qualify if:

• Patients with BCR-ABL other than M-BCR-ABL, Philadelphia negative CML.
• Patients previously treated with Tyrosine Kinase Inhibitors (TKIs).
• Medical history and concurrent diseases :
• Hypersensitivity to any of the excipients of dasatinib
• Prior treatment with Interferon-α, contraindication to interferon-α, hypersensitivity to any of the excipients of PegIFNα2b,
• Concomitant immunosuppressive treatment or corticosteroids,
• Preexisting thyroid disease unless it is controlled with conventional treatment, Auto-immune thyroiditis,
• Autoimmune disorder, Chronic liver disease,
• Prior or ongoing severe psychiatric disease,
• Epilepsy or compromised central nervous system(CNS) function,
• HIV positivity, chronic hepatitis B or C,
• Uncontrolled or significant cardio vascular or pulmonary disease,
• 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.
• Prohibited treatments and/or therapies:
• strong inhibitors of the CYP3A4,

Sponsors & Collaborators

• Poitiers University Hospital: lead

Related Publications (1)

• Roy L, Chomel JC, Guilhot J, Guerci-Bresler A, Escoffre-Barbe M, Giraudier S, Charbonnier A, Dubruille V, Huguet F, Johnson-Ansah H, Lenain P, Ame S, Etienne G, Nicolini FE, Rea D, Cony-Makhoul P, Courby S, Ianotto JC, Legros L, Machet A, Coiteux V, Hermet E, Cayssials E, Bouchet S, Mahon FX, Rousselot P, Guilhot F; French CML Group (FiLMC). Dasatinib plus Peg-Interferon alpha 2b combination in newly diagnosed chronic phase chronic myeloid leukaemia: Results of a multicenter phase 2 study (DASA-PegIFN study). Br J Haematol. 2023 Jan;200(2):175-186. doi: 10.1111/bjh.18486. Epub 2022 Oct 10.

  PMID: 36214090 DERIVED

MeSH Terms

Interventions

Dasatinib; peginterferon alfa-2b

Intervention Hierarchy (Ancestors)

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

Study Officials

• Lydia ROY, MD

  Poitiers University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2013
• First Posted: June 7, 2013
• Study Start: October 15, 2013
• Primary Completion: October 31, 2018
• Study Completion: October 31, 2018
• Last Updated: February 10, 2020

Record last verified: 2020-02