Exploratory Study of Inecalcitol in Imatinib-TreatedResidual Chronic Myeloid Leukaemia: INIM Study

Phase 1

• Conditions: Residual disease in Chronic Myeloid Leukaemia; MedDRA version: 18.0Level: LLTClassification code 10009015Term: Chronic myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2014-004347-12-FR
• Lead Sponsor: Hybrigenics SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-19
• Last Update Posted: 23 July 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 54

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 ou 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;
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 54
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 54

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 from 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, bisphosphonates, and 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;

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of inecalcitol in combination with imatinib in chronic myeloid leukaemia patients with molecular residual disease on imatinib monotherapy.;Secondary Objective: To determine:<br>- duration of response<br>- progression free survival<br>- proportion of responders during inecalcitol treatment and 2 years after discontinuation of inecalcitol and imatinib<br>- bone remodeling effect<br>- safety of inecalcitol in combination with imatinib<br>- quality of life;Primary end point(s): Proportion of responders defined as patients achieving at least MR4.5 (i.e. detectable disease = 0.0032 % BCR-ABL IS or undetectable disease with cDNA with =32,000 ABL1 transcripts) at any time within 12 months after the initiation of inecalcitol.;Timepoint(s) of evaluation of this end point: At 6 months and then at least every 3 months or every month for patient achieving MR4,5.