Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    ACTIW
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02767063
Recruitment Status : Recruiting
First Posted : May 10, 2016
Last Update Posted : May 24, 2018
Sponsor:
Information provided by (Responsible Party):
Philippe ROUSSELOT, Versailles Hospital

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.


Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Chronic-Phase Drug: Pioglitazone Drug: Avelumab Phase 1 Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Candidate Therapies in Combination or Sequentially With Tyrosine Kinase Inhibitors in Chronic Phase-chronic Myelogenous Leukemia Patients in CCR Without Achieving a Deep Molecular Response: an Adaptative Trial Based on a Drop Loser Design
Study Start Date : July 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
Experimental: Experimental Arm_ACTOS

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
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.

No Intervention: controled Arm
TKI : Daily dose and schedule identical to the daily dose and schedule administered during the last 3 months
Experimental: Experimental Arm_AVELUMAB
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
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)




Primary Outcome Measures :
  1. Cumulative incidence of patients achieving a deep molecular response [ Time Frame: 12 months ]
    The cumulative incidence of patients achieving a deep molecular response defined by MR4.5 or deeper (BCR-ABLIS ≤ 0.0032 %) by 12 months


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 12 Months ]
    Adverse events

  2. The cumulative rate of patients achieving MR4.5 by 24months in experimental and control arms [ Time Frame: 24 months ]
    The cumulative rate of patients achieving MR4.5 by 24months in experimental and control arms

  3. The cumulative rate of patients achieving MR4.5 by 36 months in experimental and control arms [ Time Frame: 36 months ]
    The cumulative rate of patients achieving MR4.5 by 36 months in experimental and control arms

  4. The cumulative rate of patients achieving MR4.5 by 48 months in experimental and control arms [ Time Frame: 48 months ]
    The cumulative rate of patients achieving MR4.5 by 48months in experimental and control arms

  5. The cumulative rate of patients achieving MR4 by 12months in experimental and control arms [ Time Frame: 12 months ]
    The cumulative rate of patients achieving MR4 by 12,months in experimental and control arms

  6. The cumulative rate of patients achieving MR4 by 24 months in experimental and control arms [ Time Frame: 24 months ]
    The cumulative rate of patients achieving MR4 by 24 months in experimental and control arms

  7. The cumulative rate of patients achieving MR4 by 36 months in experimental and control arms [ Time Frame: 36 months ]
    The cumulative rate of patients achieving MR4 by 36 months in experimental and control arms

  8. The cumulative rate of patients achieving MR4 by 48 months in experimental and control arms [ Time Frame: 48 months ]
    The cumulative rate of patients achieving MR4 by 48 months in experimental and control arms

  9. The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 12months in experimental and control arms [ Time Frame: 12 months ]
    The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 12months in experimental and control arms

  10. The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 24months in experimental and control arms [ Time Frame: 24 months ]
    The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 24, months in experimental and control arms

  11. The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 36 months in experimental and control arms [ Time Frame: 36 months ]
    The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 36 months in experimental and control arms

  12. The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 48 months in experimental and control arms [ Time Frame: 48 months ]
    The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 48 months in experimental and control arms

  13. The rate of patients in treatment free remission during follow-up [ Time Frame: 48 months ]
    The rate of patients in treatment free remission during follow-up

  14. Quantification of CML- and normal-CFU in bone marrow by clonogenic assays and RTQ- PCR [ Time Frame: 12 months ]
  15. Survival [ Time Frame: 48 months ]
    Survival

  16. duration of response [ Time Frame: 48 months ]
    duration of response

  17. event free survival [ Time Frame: 48 months ]
    event free survival

  18. progression free survival [ Time Frame: 48 months ]
    progression free survival



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Common Inclusion Criteria:

  1. Patient aged 18y or more
  2. Signed informed consent
  3. Patient with Philadelphia chromosome positive chronic phase CML and M BCR-ABL1 transcript positivity at diagnosis
  4. Treatment with imatinib, nilotinib, dasatinib or bosutinib for more than 2 years overall
  5. No switch between tyrosine kinase inhibitors within the last 3 months
  6. No dose modification within the last 3 months
  7. Complete cytogenetic response or BCR-ABL1IS ≤ 1%
  8. Detectable BCR-ABL1 with BCR-ABL1IS > 0.0032% (less than MR4.5)
  9. ECOG grade 0 to 2
  10. ASAT and ALAT ≤ 2.5 N
  11. Bilirubin in serum ≤ 2.5 N
  12. Men and Women of childbearing potential must be using an adequate method of contraception

These specific inclusion criteria will apply for the Avelumab arm in addition to the common criteria.

  1. Hematologic:

    1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L,
    2. Platelet count ≥ 100 × 109/L,
    3. Hemoglobin ≥ 9 g/dL. (may have been transfused).
  2. Hepatic:

    a. Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range.

  3. Renal: Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
  4. Pregnancy test: Negative serum or urine pregnancy test at screening for women of childbearing potential.
  5. Contraception: Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last Avelumab treatment administration if the risk of conception exists.

Common Exclusion Criteria:

  1. Pregnant or lactating women,
  2. Participation in another clinical trial with any investigative drug within 30 days prior to study enrolment,
  3. Prior history of hematopoietic stem cell transplantation (autologous or allogenic)
  4. 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
  5. Grade III or IV fluid retention
  6. Known BCR-ABL kinase domain mutation
  7. CML patient not in chronic phase at diagnosis
  8. Individuals with an active malignancy
  9. Known HIV-positivity

These specific exclusion criteria will apply for the pioglitazone arm in addition to the common criteria.

  1. Known osteoporosis with curative therapy (prophylactic therapy is not an exclusion criteria)
  2. Patient requiring anti-diabetic medication

These specific exclusion criteria will apply for the Avelumab arm in addition to the common criteria:

  1. IMMUNOSUPRESSANTS: Current use of immunosuppressive medication, EXCEPT for the following:

    1. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
    2. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
    3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  2. AUTOIMMUNE DISEASE: Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  3. ORGAN TRANSPLANTATION: Prior organ transplantation including allogenic stem-cell transplantation.
  4. INFECTIONS: Active infection requiring systemic therapy.
  5. HIV/AIDS: Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
  6. HEPATITIS: Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
  7. VACCINATION: Vaccination within 4 weeks of the first dose of Avelumab and while on trials is prohibited except for administration of inactivated vaccines
  8. HYPERSENSITIIVTY TO STUDY DRUG: Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions tomonoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
  9. CARDIOVASCULAR DISEASE: Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia equiring medication.
  10. OTHER PERSISTING TOXICITIES: Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
  11. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this 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): NCT02767063


Contacts
Layout table for location contacts
Contact: Laure MORISSET 003339239785 lmorisset@ch-versailles.fr

Locations
Layout table for location information
France
Martine GARDEMBAS Recruiting
Angers, France
Contact: Martine GARDEMBAS    02.41.35.44.75    MaGardembas@chu-angers.fr   
Pascale CONY.MAKHOUL Recruiting
Annecy, France
Contact: Pascale CONY.MAKHOUL    04.50.63.64.31    pconymakhoul@ch-annecygenevois.fr   
Thorsten BRAUN Recruiting
Bobigny, France
Contact: Thorsten BRAUN    01.48.95.54.58    Thorsten.braun@avc.aphp.fr   
Etienne Recruiting
Bordeaux, France
Contact: Gabriel Etienne    05.56.33.04.76    G.Etienne@bordeaux.unicancer.fr   
CHU Côte de Nacre Not yet recruiting
Caen, France
Contact: Hyacynthe Johnson-Ansah    02.31.27.25.39    Johnsonansah-a@chu-caen.fr   
CHU Estaing Not yet recruiting
Clermont-Ferrand, France
Contact: Marc BERGER       mberger@chu-clermontferrand.fr   
CH Henri Mondor Recruiting
Créteil, France
Contact: ROY Lydia         
Rousselot Recruiting
Le Chesnay, France
Contact: Philippe Rousselot    01.39.63.89.09    phrousselot@ch-versailles.fr   
CHU Lille Recruiting
Lille, France
Contact: COITEUX Valérie         
CHU de LIMOGES Not yet recruiting
Limoges, France
Contact: Amélie PENOT    05.55.05.66.42    Amelie.penot@chu-limoges.fr   
Franck NICOLINI Recruiting
Lyon, France
Contact: Franck NICOLINI    04.72.11.74.01    franck.nicolini@chu-lyon.fr   
Institut P Calmette Recruiting
Marseille, France
Contact: CHARBONNIER Aude         
Viviane DUBRUILLE Recruiting
Nantes, France
Contact: Viviane DUBRUILLE    02.40.08.32.71    Viviane.dubruille@chu-nantes.fr   
Hopital l'Archet Not yet recruiting
Nice, France
Contact: Laurence LEGROS    04.92.03.58.41    legros.l@chu-nice.fr   
Eric JOURDAN Recruiting
Nimes, France
Contact: Eric JOURDAN    04.66.68.32.31    eric.jourdan@chu-nimes.fr   
Hôpital La Source Recruiting
Orléans, France
Contact: BENBRAHIM Omar         
Delphine REA _St louis Recruiting
Paris, France
Contact: Delphine REA    01.42.49.96.49    delphine.rea@aphp.fr   
Simona LAPUSAN_St Antoine Recruiting
Paris, France
Contact: Simona LAPUSAN    01.49.28.34.42    Simona.lapusan@sat.aphp.fr   
Cayssials Recruiting
Poitiers, France
Contact: Emilie Cayssials    : 05.49.44. 44.72    e.cayssials@chu-poitiers.fr   
CHU de Rennes - Pontchaillou Recruiting
Rennes, France
Contact: ESCOFFRE-BARBE Martine         
Hôpital René Huguenin Not yet recruiting
Saint-Cloud, France
Contact: Sylvie GLAISNER    01.47.11.15.30    Sylvie.glaisner@curie.net   
Institut Universitaire contre le Cancer Not yet recruiting
Toulouse, France
Contact: Françoise HUGUET    05.31.15.63.56    Huguet.françoise@iuct-oncopole.fr   
CHU Tours Not yet recruiting
Tours, France
Contact: DARTIGEAS Caroline         
Sponsors and Collaborators
Versailles Hospital
Investigators
Layout table for investigator information
Principal Investigator: Philippe ROUSSELOT CH Versailles

Layout table for additonal information
Responsible Party: Philippe ROUSSELOT, Clinical coordinator, Versailles Hospital
ClinicalTrials.gov Identifier: NCT02767063     History of Changes
Other Study ID Numbers: P13/12_ACTIW
First Posted: May 10, 2016    Key Record Dates
Last Update Posted: May 24, 2018
Last Verified: May 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs