PIOGLITAZONE for Chronic myelogenous leukaemia (chronic phase)

Inclusion criteria

• {"criterion_text":"- Patient aged 18y or more\n- ASAT and ALAT ≤ 2.5 N\n- Bilirubin in serum ≤ 2.5 N\n- Men and Women of childbearing potential must be using an adequate method of contraception\n- Hematologic: a. Absolute neutrophil count (ANC) ≥ 1.5 × 109 /L, b. Platelet count ≥ 100 × 109 /L, c. Hemoglobin ≥ 9 g/dL. (may have been transfused). (avelumab arm only)\n- Hepatic: a. Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range. (Avelumab arm only)\n- Renal: Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) (avelumab arm only)\n- Pregnancy test: Negative serum or urine pregnancy test at screening for women of childbearing potential. (avelumab arm only)\n- 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 (avelumab arm only)\n- Signed informed consent\n- Patient with chronic phase CML and M BCR-ABL1 transcript positivity\n- Treatment with imatinib, nilotinib, dasatinib, bosutinib for more than 2 years overall\n- No switch between tyrosine kinase inhibitors within the last 3 months\n- No dose modification within the last 3 months\n- Complete cytogenetic response or BCR-ABLIS ≤ 1%\n- Detectable BCR-ABL1 with BCR-ABLIS > 0.0032% (less than MR4.5)\n- ECOG grade 0 to 2"}

Exclusion criteria

• {"criterion_text":"- Pregnant or lactating women\n- Known osteoporosis with curative therapy (prophylactic therapy is not an exclusion criteria) - (Pioglitazone arm only)\n- Patient requiring anti-diabetic medication (pioglitazone arm only)\n- IMMUNOSUPRESSANTS (Avelumab arm only): Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).\n- AUTOIMMUNE DISEASE (Avelumab arm only): 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.\n- ORGAN TRANSPLANTATION (Avelumab arm only): Prior organ transplantation including allogenic stem-cell transplantation.\n- INFECTIONS (Avelumab arm only): Active infection requiring systemic therapy.\n- HIV/AIDS (Avelumab arm only): Known history of testing positive for HIV or known acquired immunodeficiency syndrome.\n- HEPATITIS (Avelumab arm only): 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)\n- VACCINATION (avelumab arm only): Vaccination within 4 weeks of the first dose of Avelumab and while on trials is prohibited except for administration of inactivated vaccines\n- HYPERSENSITIIVTY TO STUDY DRUG (Avelumab arm only): Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)\n- Participation in another clinical trial with any investigative drug within 30 days prior to study enrolment\n- OTHER PERSISTING TOXICITIES (AVelumab arm only): 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\n- 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. (avelumab arm only)\n- Prior history of hematopoietic stem cell transplantation (allogenic)\n- 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\n- Grade III or IV fluid retention\n- Known BCR-ABL kinase domain mutation\n- Absence de phase chronique lors du diagnostic de la LMC\n- Individuals with an active malignancy\n- Known HIV-positivity"}

Primary endpoints

• {"endpoint_text":"- The primary end-point is the cumulative incidence of patients achieving a deep molecular response defined by MR4.5 or deeper (BCR-ABLIS ≤ 0.0032 %) by 12 months.","definition_or_measurement_approach":"Defined by MR4.5 (BCR-ABLIS ≤ 0.0032%) measured by standardized BCR-ABL IS assay; reported as cumulative incidence by 12 months."}

Secondary endpoints

• {"endpoint_text":"- Adverse events","definition_or_measurement_approach":"Safety assessed by recording adverse events (no further definition in provided data)."}
• {"endpoint_text":"- The cumulative rate of patients achieving MR4.5 by 24, 36, 48 months in experimental and control arms","definition_or_measurement_approach":"Cumulative incidence of MR4.5 at specified timepoints (24, 36, 48 months) measured by BCR-ABL IS."}
• {"endpoint_text":"- The cumulative rate of patients achieving MR4 by 12, 24, 36, 48 months in experimental and control arms","definition_or_measurement_approach":"Cumulative incidence of MR4 at specified timepoints measured by BCR-ABL IS."}
• {"endpoint_text":"- The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 12, 24, 36, 48 months in experimental and control arms","definition_or_measurement_approach":"Undetectable BCR-ABL1 defined at assay sensitivity of 40000 ABL copies, assessed at 12, 24, 36, 48 months."}
• {"endpoint_text":"- The rate of patients in treatment free remission during follow-up","definition_or_measurement_approach":"Proportion of patients achieving treatment-free remission during follow-up (no further specification provided)."}
• {"endpoint_text":"- Measurement of number and clonogenicity of CML stem cells using the leukemic stem cell markers followed by flow cytometry analysis and the LTC-IC assay and others markers (ancillary study)","definition_or_measurement_approach":"Ancillary study: quantification by flow cytometry and LTC-IC assay to measure number and clonogenicity of leukemic stem cells."}
• {"endpoint_text":"- Survival, progression free survival, event free survival, duration of response","definition_or_measurement_approach":"Standard time-to-event endpoints (overall survival, progression-free survival, event-free survival, duration of response) — no further details provided."}

France

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

16-09-2024

Processing Time Days

10

Number Of Sites

25

Number Of Participants

250

Primary sponsor

Full Name

Centre Hospitalier De Versailles

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France