CML, Chronic Phase
Conditions
Brief summary
To assess the efficacy of inecalcitol in combination with imatinib in CML patients with molecular residual disease on imatinib monotherapy.
Detailed description
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
Interventions
DRUGInecalcitol
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.
Sponsors
Hybrigenics Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure the proportion of responders | 12 months | 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. |
Countries
France
Contacts
Primary ContactJean-Francois Dufour-Lamartinie, MD
Outcome results
None listed