Imatinib Mesylate and Zoledronic Acid in Patients With Chronic Myeloid Leukaemia in Cytogenetic Response Without Molecular Response
Condition: Myeloid Leukemia, Chronic
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Intervention: Glivec
Intervention MeSH terms: Imatinib Mesylate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic myeloid leukemia; imatinib mesylate; zoledronate; molecular response

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