Therapies in Combination or Sequentially With Tyrosine Kinase Inhibitors (TKIs) in Chronic Phase Chronic Myelogenous Leukemia Patients in CCR (ACTIW)

NCT02767063 | Unknown Phase 1 DMC

• 1 other identifier: P13/12_ACTIW
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 23

Brief Summary

Patients will be randomized in phase II trials to continue on the same TKI versus one of the alternative treatment approaches. If a patient is not eligible for one of the treatments, he (she) will be randomized between the options for which he (she) is eligible. The trial will start with current available treatment options (experimental arms). New available treatment options may be open at any times later on. Authorized TKIs are imatinib, nilotinib, dasatinib, bosutinib and ponatinib. For all options the treatment duration is for a minimum of 12 months and will be continued in the absence of adverse events following investigator decision. Each therapeutic option will be detailed in term of combination modalities, dose, dose adaptation, specific warnings, specific exclusion and inclusion criteria. The decision to introduce a new option will depend on the general pace of recruitment and on the assessment of the potential efficacy and safety of the new treatment, and will be implemented after scientific review by a protocol amendment. Primary objective: A. To select molecules in combination or sequentially with imatinib, nilotinib, dasatinib, bosutinib or ponatinib potentially able to produce a 25% increase in the Cumulative Incidence of MR4.5 as compare to control. Secondary objectives: A. To determine the safety of selected therapies B. To determine the rate of MR4 by 12, 24, 36, 48 months in experimental and control arms C. To determine the rates of MR4.5 by 24, 36, 48 months in experimental and control arms D. To determine the rate of undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 12, 24, 36, 48 months in experimental and control arms E. To estimate treatment free remission (TFR) in patients eligible for discontinuation studies F. To investigate the relationship between biological activity and the clinical efficacy of the selected therapies G. To assess the effects of the treatments on the number and clonogenicity of CML stem cells and other biological markers of interest H. To estimate duration of response, progression-free survival, event free survival and overall survival.

Conditions

Leukemia, Myeloid, Chronic-Phase

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of patients achieving a deep molecular response

  The cumulative incidence of patients achieving a deep molecular response defined by MR4.5 or deeper (BCR-ABLIS ≤ 0.0032 %) by 12 months

  12 months

Secondary Outcomes (18)

• Adverse events

  12 Months

• The cumulative rate of patients achieving MR4.5 by 24months in experimental and control arms

  24 months

• The cumulative rate of patients achieving MR4.5 by 36 months in experimental and control arms

  36 months

• The cumulative rate of patients achieving MR4.5 by 48 months in experimental and control arms

  48 months

• The cumulative rate of patients achieving MR4 by 12months in experimental and control arms

  12 months

Study Arms (3)

Experimental Arm_ACTOS

EXPERIMENTAL

TKI : Daily dose and schedule identical to the daily dose and schedule administered during the last 3 months PIOGLITAZONE (Actos®): 30 mg per day for 12 months. The dose will be increased to 45 mg per day after 2 months in the absence of grade \>1 related AE.

Drug: Pioglitazone

controled Arm

NO INTERVENTION

TKI : Daily dose and schedule identical to the daily dose and schedule administered during the last 3 months

Experimental Arm_AVELUMAB

EXPERIMENTAL

TKI : Daily dose and schedule identical to the daily dose and schedule administered during the last 3 months AVELUMAB: 10mg/kg every 2 weeks, for a maximum of 8 IV infusions over a 4 months' period.(If MR4.5 is acheived by the first 3 months the 7th and 8th infusions will be omitted)

Drug: Avelumab

Interventions

Pioglitazone DRUG

PIOGLITAZONE (Actos®): 30 mg per day for 12 months. The dose will be increased to 45 mg per day after 2 months in the absence of grade \>1 related AE.

Experimental Arm_ACTOS

Avelumab DRUG

10mg/kg every 2 weeks, for a maximum of 8 IV infusions over a 4 months' period. (If MR4.5 is acheived by the first 3 months the 7th and 8th infusions will be omitted)

Experimental Arm_AVELUMAB

Eligibility Criteria

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

You may qualify if:

• Patient aged 18y or more
• Signed informed consent
• Patient with Philadelphia chromosome positive chronic phase CML and M BCR-ABL1 transcript positivity at diagnosis
• Treatment with imatinib, nilotinib, dasatinib or bosutinib for more than 2 years overall
• No switch between tyrosine kinase inhibitors within the last 3 months
• No dose modification within the last 3 months
• Complete cytogenetic response or BCR-ABL1IS ≤ 1%
• Detectable BCR-ABL1 with BCR-ABL1IS \> 0.0032% (less than MR4.5)
• ECOG grade 0 to 2
• ASAT and ALAT ≤ 2.5 N
• Bilirubin in serum ≤ 2.5 N
• Men and Women of childbearing potential must be using an adequate method of contraception
• Hematologic:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L,
• Platelet count ≥ 100 × 109/L,

You may not qualify if:

• Pregnant or lactating women,
• Participation in another clinical trial with any investigative drug within 30 days prior to study enrolment,
• Prior history of hematopoietic stem cell transplantation (autologous or allogenic)
• Cardiovascular disease:
• Stage II to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system for heart failure.
• Myocardial infarction within the previous 6 months
• Symptomatic cardiac arrhythmia requiring treatment
• Grade III or IV fluid retention
• Known BCR-ABL kinase domain mutation
• CML patient not in chronic phase at diagnosis
• Individuals with an active malignancy
• Known HIV-positivity
• Patient requiring anti-diabetic medication
• IMMUNOSUPRESSANTS: Current use of immunosuppressive medication, EXCEPT for the following:
• intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);

Sponsors & Collaborators

• Versailles Hospital: lead

Study Sites (23)

Martine GARDEMBAS

Angers, France

RECRUITING

Pascale CONY.MAKHOUL

Annecy, France

RECRUITING

Thorsten BRAUN

Bobigny, France

RECRUITING

Etienne

Bordeaux, France

RECRUITING

CHU Côte de Nacre

Caen, France

NOT YET RECRUITING

CHU Estaing

Clermont-Ferrand, France

NOT YET RECRUITING

CH Henri Mondor

Créteil, France

RECRUITING

Rousselot

Le Chesnay, France

RECRUITING

CHU Lille

Lille, France

RECRUITING

CHU de LIMOGES

Limoges, France

NOT YET RECRUITING

Franck NICOLINI

Lyon, France

RECRUITING

Institut P Calmette

Marseille, France

RECRUITING

Viviane DUBRUILLE

Nantes, France

RECRUITING

Hopital l'Archet

Nice, France

NOT YET RECRUITING

Eric JOURDAN

Nîmes, France

RECRUITING

Hôpital La Source

Orléans, France

RECRUITING

Delphine REA _St louis

Paris, France

RECRUITING

Simona LAPUSAN_St Antoine

Paris, France

RECRUITING

Cayssials

Poitiers, France

RECRUITING

CHU de Rennes - Pontchaillou

Rennes, France

RECRUITING

Hôpital René Huguenin

Saint-Cloud, France

NOT YET RECRUITING

Institut Universitaire contre le Cancer

Toulouse, France

NOT YET RECRUITING

CHU Tours

Tours, France

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase

Interventions

Pioglitazone; avelumab

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)

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

Study Officials

• Philippe ROUSSELOT

  CH Versailles

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laure MORISSET

CONTACT

003339239785; lmorisset@ch-versailles.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical coordinator

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: May 10, 2016
• Study Start: July 1, 2016
• Primary Completion: November 1, 2022
• Study Completion: June 1, 2023
• Last Updated: August 7, 2020

Record last verified: 2020-08

Locations

FR (23)