Efficacy Study of Inecalcitol With Decitabine in Acute Myeloid Leukemia Patients Unfit for Standard Chemotherapy

Study Overview
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Brief Summary
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Evaluate the effect of the addition of inecalcitol to decitabine treatment on overall survival in previously untreated AML patients aged 65 years or more who are randomly assigned to receive decitabine with or without inecalcitol.

Official Title
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Efficacy Study of Inecalcitol in Combination With Decitabine in Acute Myeloid Leukemia Patients Unfit for Standard Chemotherapy

Conditions
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Acute Myelogenous Leukemia

Intervention / Treatment
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* Drug: Inecalcitol
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Patients aged 65 to < 75 years with at least one non severe comorbidity ie disease or syndrome with mild to moderate clinical or diagnostic observations or lab abnormalities which could increase the risk of toxicity and/or early death of intensive chemotherapy in the opinion of the investigator and are not contra-indicated for non-intensive chemotherapy. or ≥ 75 years with or without any comorbidity at the time of the informed consent signature; • Newly diagnosed, untreated de novo or secondary AML according to WHO classification; Exclusion Criteria: Prior or current treatment with chemotherapy for any myeloid disorder (excluding hydroxyurea) or radiotherapy for extramedullary involvement within 2 weeks of randomization; Prior treatment with decitabine, azacitidine, or cytarabine; Prior malignancies for 5 years with exception of basal cell, squamous cell carcinoma of the skin, or carcinoma  in situ  of the cervix or breast; Chronic myelogenous or acute promyelocytic leukaemia; Known CNS involvement; Patient eligible to bone marrow or stem cell transplant; WBC ≥ 30.000/mm3; Impaired renal function with Creatinine clearance < 30 mL/min/1.73m² according to the MDRD formula; Serum bilirubin ≥ 2.5 x ULN and/or AST and/or ALT ≥ 2.5 x ULN (upper limit of normal value); Calcemia ≥ 2.65 mmol/L (106 mg/L) at screening assessment (corrected with albuminemia); History of diseases known to be associated with calcium disorders: ongoing hyperparathyroidism, sarcoidosis….; Presence or history of symptomatic kidney stones in the last 5 years; Hypersensitivity to any of the excipients of decitabine (Potassium dihydrogen phosphate (E340) ; Sodium hydroxide (E524) ; Hydrochloric acid (for pH adjustment) or to the excipient of inecalcitol tablets (lactose); Current use of drugs known to influence serum calcium (such as thiazide diuretics, teriparatide, calcitonin and multivitamin supplements containing > 400 IU of vitamin D or calcium); Current use of digitalis; Current use of drugs which could influence bioavailability of inecalcitol (such as magnesium-containing antacids, bile-resin binders); Use of any other experimental drug or therapy or vitamin D supplementation within 4 weeks of randomization; Known HIV; Patients who are eligible for intensive induction therapy with curative intent; Refractory congestive heart failure; Active infection resistant to anti-infective therapy; Documented pulmonary disease with DLCO ≤ 65% or FEV1≤ 65%, or dyspnea at rest or requiring oxygen, or any pleural neoplasm or uncontrolled lung neoplasm; Liver cirrhosis Child B or C or acute viral hepatitis; Current mental illness requiring psychiatric hospitalization, institutionalization or intensive outpatient management, or current cognitive status that produces dependence (as confirmed by the specialist) not controlled by the caregiver; Uncontrolled neoplasia;

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: inecalcitol<br>Two tablets of Inecalcitol 2mg each (total 4mg) taken orally every other day. | Drug: Inecalcitol<br>* vitamin D receptor agonist<br>|
| Placebo Comparator: placebo<br>Two tablets of placebo 2mg each (total 4mg) taken orally every other day | Drug: Placebo Oral Tablet<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 24 months |