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Imatinib Mesylate and Zoledronic Acid in Patients With Chronic Myeloid Leukaemia in Cytogenetic Response Without Molecular Response (AFR22)

Primary Purpose

Myeloid Leukemia, Chronic

Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Glivec
Sponsored by
Institut Bergonié
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myeloid Leukemia, Chronic focused on measuring Chronic myeloid leukemia, imatinib mesylate, zoledronate, molecular response

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Centre Hospitalier Universitaire de Bordeaux
  • Institut Bergonié - Centre Régional de Luttre Contre le Cancer de Bordeaux et du Sud Ouest
  • Centre Hospitalier de Versailles
  • Hôpital Edouard Herriot
  • Hôpital Archet
  • Hôpital Saint Louis
  • Centre Hospitalier Universitaire de Poitiers

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Imatinib mesylate

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
September 12, 2005
Last Updated
November 5, 2021
Sponsor
Institut Bergonié
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00210119
Brief Title
Imatinib Mesylate and Zoledronic Acid in Patients With Chronic Myeloid Leukaemia in Cytogenetic Response Without Molecular Response
Acronym
AFR22
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

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Terminated
Study Start Date
July 12, 2006 (Actual)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Institut Bergonié
Collaborators
Novartis

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myeloid Leukemia, Chronic
Keywords
Chronic myeloid leukemia, imatinib mesylate, zoledronate, molecular response

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Imatinib mesylate
Arm Type
Experimental
Arm Description
Imatinib mesylate 600 or 800 mg/day PO + zoledronate 4 mg IV over 15 min every 3 weeks for 6 months.
Intervention Type
Drug
Intervention Name(s)
Glivec
Primary Outcome Measure Information:
Title
Percentage of Participants With Molecular Response
Description
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
Secondary Outcome Measure Information:
Title
Percentage of Participants With a Reduction of BCR-ABL Transcript Level > 4.5 Log From the Start of From Initiation of Treatment
Description
reduction of BCR-ABL transcript level > 4.5 Log from the start of from initiation of treatment
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Josy REIFFERS, Pr
Organizational Affiliation
Institut Bergonié
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier Universitaire de Bordeaux
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Institut Bergonié - Centre Régional de Luttre Contre le Cancer de Bordeaux et du Sud Ouest
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Centre Hospitalier de Versailles
City
Le Chesnay
ZIP/Postal Code
78150
Country
France
Facility Name
Hôpital Edouard Herriot
City
Lyon
ZIP/Postal Code
69437
Country
France
Facility Name
Hôpital Archet
City
Nice
ZIP/Postal Code
06200
Country
France
Facility Name
Hôpital Saint Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Centre Hospitalier Universitaire de Poitiers
City
Poitiers
ZIP/Postal Code
86000
Country
France

12. IPD Sharing Statement

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

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