Myeloid Leukemia, Chronic
Conditions
Keywords
Chronic myeloid leukemia, imatinib mesylate, zoledronate, molecular response
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.
Interventions
DRUGGlivec
Sponsors
Novartis
Institut Bergonié
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
France
Participant flow
Recruitment details
The AFR-22 trial was based on a two-stage Simon's design, which included 17 patients in the first stage, followed by an additional 20 patients. Analysis of the first 17 evaluable patients showed insufficient efficacy of the study treatment. In accordance with the principle of Simon's two-stage design, enrollment was stopped.
Participants by arm
| Arm | Count |
|---|---|
| Imatinib Mesylate Imatinib mesylate 600 or 800 mg/day PO + zoledronate 4 mg IV over 15 min every 3 weeks for 6 months.
Glivec | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Imatinib Mesylate |
|---|---|
| Age, Continuous | 58.4 years |
| Region of Enrollment France | 19 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 1 / 17 |
Outcome results
Primary
Percentage of Participants With Molecular Response
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
Time frame: 6 months
Population: 2 patients were not assessable for the primary outcome measure : 1 not eligible and 1 not treated because of withdrawal
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imatinib Mesylate | Percentage of Participants With Molecular Response | 0 percentage of participants |
Secondary
Percentage of Participants With a Reduction of BCR-ABL Transcript Level > 4.5 Log From the Start of From Initiation of Treatment
reduction of BCR-ABL transcript level \> 4.5 Log from the start of from initiation of treatment
Time frame: 6 months
Population: 2 patients were not assessable for secondary outcome measures
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imatinib Mesylate | Percentage of Participants With a Reduction of BCR-ABL Transcript Level > 4.5 Log From the Start of From Initiation of Treatment | 0 percentage of participants |