Imatinib Mesylate and Zoledronic Acid in Patients With Chronic Myeloid Leukaemia in Cytogenetic Response Without Molecular Response

Phase 2

Terminated

• Conditions: Myeloid Leukemia, Chronic
• Interventions: Drug: Glivec

• Registration Number: NCT00210119
• Lead Sponsor: Institut Bergonié

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2005-09-12
• Study First Submitted QC: 2005-09-13
• Study First Posted: 2005-09-21
• Study Start: 2006-07-12
• Primary Completion: 2007-09
• Study Completion: 2009-03
• Status Verified: 2021-09
• Results First Submitted: 2021-09-29
• Results First Submitted QC: 2021-09-29
• Results First Posted: 2021-10-28
• Last Update Submitted: 2021-11-05
• Last Update Posted: 2021-11-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 19

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Imatinib mesylate	Glivec	Imatinib mesylate 600 or 800 mg/day PO + zoledronate 4 mg IV over 15 min every 3 weeks for 6 months.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Molecular Response	6 months	A patient is considered to be in molecular response if at least one of the following conditions is observed : - a complete molecular response at 6 months defined by PCR negativation tested on twice; OR; - reduction of BCR-ABL transcript level \> 2 Log from the start of from initiation of treatment

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With a Reduction of BCR-ABL Transcript Level > 4.5 Log From the Start of From Initiation of Treatment	6 months	reduction of BCR-ABL transcript level \> 4.5 Log from the start of from initiation of treatment

Trial Locations

Locations (7)

Hôpital Archet; 🇫🇷 Nice, France

Centre Hospitalier Universitaire de Poitiers; 🇫🇷 Poitiers, France

Centre Hospitalier Universitaire de Bordeaux; 🇫🇷 Bordeaux, France

Institut Bergonié - Centre Régional de Luttre Contre le Cancer de Bordeaux et du Sud Ouest; 🇫🇷 Bordeaux, France

Centre Hospitalier de Versailles; 🇫🇷 Le Chesnay, France

Hôpital Edouard Herriot; 🇫🇷 Lyon, France

Hôpital Saint Louis; 🇫🇷 Paris, France