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

• Sponsor: Institut Bergonié (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00210119
• Collaborator: Novartis (Industry)
• Enrollment: 19
• Locations: 7
• Arm: 1
• Actual Duration (Months): 31.6
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Myeloid Leukemia, Chronic	Drug: Glivec	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jul 12, 2006
• Actual Primary Completion Date: Sep 1, 2007
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Imatinib mesylate Imatinib mesylate 600 or 800 mg/day PO + zoledronate 4 mg IV over 15 min every 3 weeks for 6 months.	Drug: Glivec

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre Hospitalier Universitaire de Bordeaux	Bordeaux		France	33076
2	Institut Bergonié - Centre Régional de Luttre Contre le Cancer de Bordeaux et du Sud Ouest	Bordeaux		France	33076
3	Centre Hospitalier de Versailles	Le Chesnay		France	78150
4	Hôpital Edouard Herriot	Lyon		France	69437
5	Hôpital Archet	Nice		France	06200
6	Hôpital Saint Louis	Paris		France	75010
7	Centre Hospitalier Universitaire de Poitiers	Poitiers		France	86000

Sponsors and Collaborators

• Institut Bergonié
• Novartis

Investigators

• Principal Investigator: Josy REIFFERS, Pr, Institut Bergonié

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00210119
• Other Study ID Numbers: IB2005-25; AFR22
• First Posted: Sep 21, 2005
• Last Update Posted: Nov 8, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by , ,: Chronic myeloid leukemia; imatinib mesylate; zoledronate; molecular response
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Imatinib Mesylate

Study Results

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.

Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate 600 or 800 mg/day PO + zoledronate 4 mg IV over 15 min every 3 weeks for 6 months. Glivec
Period Title: Overall Study
STARTED	19
COMPLETED	17
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate 600 or 800 mg/day PO + zoledronate 4 mg IV over 15 min every 3 weeks for 6 months. Glivec
Overall Participants	19
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58.4
Sex: Female, Male (Count of Participants)
Female	3 15.8%
Male	16 84.2%
Region of Enrollment (Count of Participants)
France	19 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

2 patients were not assessable for the primary outcome measure : 1 not eligible and 1 not treated because of withdrawal

Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate 600 or 800 mg/day PO + zoledronate 4 mg IV over 15 min every 3 weeks for 6 months. Glivec
Measure Participants	17
Number (95% Confidence Interval) [percentage of participants]	0 0%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

2 patients were not assessable for secondary outcome measures

Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate 600 or 800 mg/day PO + zoledronate 4 mg IV over 15 min every 3 weeks for 6 months. Glivec
Measure Participants	17
Number (95% Confidence Interval) [percentage of participants]	0 0%

Adverse Events

Adverse Event Reporting Description	Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate 600 or 800 mg/day PO + zoledronate 4 mg IV over 15 min every 3 weeks for 6 months. Glivec
All Cause Mortality
	Imatinib Mesylate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Imatinib Mesylate
	Affected / at Risk (%)	# Events
Total	1/17 (5.9%)
Respiratory, thoracic and mediastinal disorders
Pulmonary edema	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Imatinib Mesylate
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.