Clinical trial NCT00210119: Imatinib Mesylate and Zoledronic Acid in Patients With Chronic Myeloid Leukaemia in Cytogenetic Response Without Molecular Response
Official title: Multicentric Phase II Study to Evaluate Feasibility and Efficacy of Association of Imatinib Mesylate and Zoledronic Acid in Patients With Chronic Myeloid Leukaemia in Cytogenetic Response Without Molecular Response After One Year of Imatinib Mesylate Monotherapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myeloid Leukemia, Chronic
Keywords: Chronic myeloid leukemia
imatinib mesylate
zoledronate
molecular response
Lead sponsor: Institut Bergonié
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2005-09-21
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Imatinib mesylate is standard treatment of Chronic myeloid leukaemia, complete cytogenetic response is obtained in most of cases but molecular response concerned only a small part of the patients. To increase molecular response ratio we decided to increase imatinib dose to limited resistance to this drug and to add zoledronate for it anti tumoral activity to increase anti leukemic effect. We plan to accrue 37 patients in 5 centers. We will analyse molecular expression of BCR-ABL transcript after 6 months of treatment, safety, duration of response, VEGF expression and LTgd production.


Eligibility criteria: Inclusion Criteria:

* Inclusion criteria: at registration· Chronic myeloid leukaemia Ph+ confirmed by cytogenetic analysis or BCR-ABL translocation by molecular biology· Chronic phase:-\<15% blast cells in blood and 5% in bone marrow-\<30% blast cells+promyelocyte cells in blood and bone marrow-\<20% basophils in blood-\>100.000 platelets· Without extra medullar attempt excepted hepatosplenomagalia· First line of treatment· Biology and biochemistry with normal levels· Male or female\>18 years old· Signed written consent· ECOG\<3At inclusion· Chronic myeloid leukaemia with cytogenetic response without molecular response after one year of treatment by imatinib and BCR-ABL transcript detected by RT-PCR

Exclusion Criteria:

* · Other cancer excepted basocellular or cervix carcinoma · Major surgery in last 2 weeks previous inclusion· Women who are pregnant or breastfeeding (are unable to use an acceptable method to avoid pregnancy of his partner for the entire study period)· Dementia or altered mental status that would prohibit the understanding or rendering of informed consent · Abnormal renal function with creatinine clearance \< 30 ml/ minuteAccording to Cockcroft-Gault : CrCl= \[\[140-age (years)\] x weight (kg)\]/ \[72 x serum creatinine (mg/dL)\] {x 0.85 for women}· Chronic myeloid leukaemia in acute phase or in pass to be in acute phase · Treatment with bisphosphonates in last 6 months previous inclusion · Intolerance to bisphosphonates: hypersensitivity, on course dental problem, including tooth or mandibular infection; dental traumatism or recent diagnosis or previous mandibular osteonecrosis, or dental extraction with cicatrisation delay or necessity to set bone evidence · Mandibular surgery in last 6 weeks or planned in the future during treatment (tooth extraction)· Serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy: diabetes, thyroid pathology, neuropsychiatric illness, myocardial infarction or congestive heart failure grade 3-4 according to " New York Heart association"· History of psychiatric or depressive pathology · HIV positivity known · Inclusion in other study investigating antineoplastic molecule in last 30 days previous inclusion

Primary outcomes:
measure: Percentage of Participants With Molecular Response
timeFrame: 6 months
Secondary outcomes:
measure: Percentage of Participants With a Reduction of BCR-ABL Transcript Level > 4.5 Log From the Start of From Initiation of Treatment
timeFrame: 6 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux
city: Bordeaux
country: France
facility: Institut Bergonié - Centre Régional de Luttre Contre le Cancer de Bordeaux et du Sud Ouest
city: Le Chesnay
country: France
facility: Centre Hospitalier de Versailles
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Nice
country: France
facility: Hôpital Archet
city: Paris
country: France
facility: Hôpital Saint Louis
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
Study officials:
affiliation: Institut Bergonié
name: Josy REIFFERS, Pr
role: PRINCIPAL_INVESTIGATOR
References: