Study to Assess Efficacy and Safety of Inecalcitol in Imatinib-Treated Residual Chronic Myeloid Leukaemia: INIM Study

Study Overview
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Brief Summary
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To assess the efficacy of inecalcitol in combination with imatinib in CML patients with molecular residual disease on imatinib monotherapy.

Detailed Description
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To determine: Duration of response Progression free survival Proportion of responders 2 years after discontinuation of inecalcitol Duration of response after discontinuation of inecalcitol and imatinib Bone remodelling effect Safety of inecalcitol in combination with imatinib Quality of Life

Official Title
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Phase 2 Study to Assess Efficacy and Safety of Inecalcitol in Imatinib-Treated Residual Chronic Myeloid Leukaemia: INIM Study

Conditions
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CML, Chronic Phase

Intervention / Treatment
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* Drug: Inecalcitol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged of at least 18 years at the time of informed consent signature; Patients have signed written informed consent; ECOG performance status < 2; Patients with Philadelphia chromosome positive chronic phase CML and M BCR-ABL transcript positivity (e13a2 or e14a2); Treatment with imatinib for more than 2 years (a history of treatment with interferon is tolerated); Patient in complete cytogenetic response with BCR-ABL/ABL status between 0.1% International Scale (IS) and 0.01% IS and no BCR-ABL checkpoint in the last six months better than Molecular Response MR4 ( i.e. BCR-ABL ratio < 0.01% IS); Women of child bearing potential have a negative pregnancy test prior to first dose and agree to practice effective contraception during the study; Fertile men agree to practice effective contraception during the study; Patients agree to comply with the study requirements and agree to come to the clinic for required study visits; Patients agree to follow medication restrictions during the study; Exclusion Criteria: Expression of unusual BCR-ABL transcripts (other than e13a2 or e14a2); Pregnant or lactating women; Participating in another clinical trial with any investigative drug within 30 days prior to study enrolment(except for OPTIM imatinib); Treatment with interferon within the last 24 months; Imatinib dose modification within the last 3 months; Prior history of haematopoietic stem cell transplantation; Impaired renal function with creatinine clearance < 30 ml/min/1.73m² according to the MDRD formula; Hypercalcemia (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; 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); Patients with a chronic condition which is not well controlled that, according to the investigator, would interfere with the completion of the study; Use of any other experimental drug, therapy or vitamin D supplementation within 30 days of first inecalcitol administration; Patients with a mental deficiency preventing proper understanding of trial protocol requirements;

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br> | Drug: Inecalcitol<br>* Prospective open label, non-comparative, multicentre exploratory study. Divided in 2 parts Part1: Inecalcitol treatment will be added to imatinib for 12 months. Part 2: Follow-up after discontinuation of inecalcitol. Imatinib will be maintained for 2 years and then will be stopped for those still in MR4.5. These patients will then be followed for 2 additional years after discontinuation of imatinib.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure the proportion of responders | Proportion of responder defined as patients achieving MR4.5 (i.e. detectable disease ≤ 0.0032 % BCR-ABLIS or undetectable disease with cDNA with ≥32,000 ABL1 transcripts) at any time within 12 months after the initiation of inecalcitol. | 12 months |