Open-Label Study Evaluating Dasatinib Therapy Discontinuation in Patients With Chronic Phase Chronic Myeloid Leukemia With Stable Complete Molecular Response

NCT ID: NCT01850004

Last Updated: 2022-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-22
• Study Completion Date: 2021-10-08

Brief Summary

The study purpose is to test the hypothesis that Chronic Phase Chronic Myeloid Leukemia (CP-CML) patients with stable Complete Molecular Response (CMR) who discontinue Dasatinib treatment are able to maintain a sustained remission in the long-term, with undetectable or minimally detectable BCR-ABL residual disease.

Detailed Description

Primary Purpose: Protocol designed to evaluate remission of disease after treatment discontinuation. Treatment re-started if relapse occurs

Conditions

Chronic Phase Chronic Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Dasatinib

Dasatinib 50, 80, 100, 140, 180 mg tablets by mouth, once daily, up to 60 months

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: DRUG

Interventions

Dasatinib

Intervention Type: DRUG

Other Intervention Names

Sprycel

Eligibility Criteria

Inclusion Criteria

• Signed Written Informed Consent
• Target Population

1. Men and women diagnosed with CP-CML, on treatment with dasatinib for a minimum of 2 years at the time of enrollment and in dasatinib-induced complete molecular remission ongoing for at least 1 year prior to study entry.

2. Patients are eligible if they have been in stable dasatinib induced CMR for a minimum of nine months, documented by at least three assessments, conducted 2 - 6.5 months apart, at a local lab.

3. Subjects who have received dasatinib beyond first or second line treatment and meet other enrollment criteria are eligible for the study provided prior Tyrosine-kinase inhibitors (TKI) were discontinued due to intolerance or lack efficacy, although only one instance of lack of efficacy to TKI is allowed.

4. Eastern Co-Operative Group (ECOG) Performance Status (PS) of 0-1

• Age and Reproductive Status

1. Men and women, ages ≥18

2. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the restart of study drug

3. Women must not be breastfeeding

4. WOCBP must agree to follow instructions for method(s) of contraception at the restart of treatment with study drug (dasatinib) and for the duration treatment plus 30 days (duration of ovulatory cycle) for a total of 30 days post-treatment completion

5. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for 90 days after study entry (withdrawal of dasatinib), at restart of study drug (dasatinib) and for the duration of treatment with study drug (dasatinib) plus 90 days (duration of sperm turnover) for a total of 90 days post-treatment completion

Exclusion Criteria

• Target Disease Exceptions

1. Patients who have not achieved a 1-log reduction in BCR-ABL transcript levels compared with baseline as determined by local standards or > 10% IS [International Standard]) documented at 3.0-6.5 months since the initial start of dasatinib therapy.

2. Patients who have previously undergone hematopoietic stem cell transplantation (SCT) or who are scheduled for SCT

3. Previous diagnosis of CML accelerated phase or blast crisis

• Medical History and Concurrent Diseases

1. Prior or concurrent malignancy, except the following:

• Curatively treated basal cell or squamous cell skin cancer
• Cervical carcinoma in situ
• Adequately treated Stage I or II cancer from which the subject is currently in complete remission
• Any other cancer from which the subject has been disease free for 3 years

2. A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy in case re-initiation of dasatinib is needed.

3. Uncontrolled or significant cardiovascular disease

4. Subjects with prior history of pericardial effusion or pleural effusion that required thoracentesis are excluded. Subjects with prior history of pericardial or pleural effusion that was clinically manageable and a maintained CMR for ≥ 1 year on a stable dose of dasatinib are allowed.

5. History of significant bleeding disorder unrelated to CML

• Allergies and Adverse Drug Reaction

a. Subjects with known hypersensitivity to excipients of Dasatinib tablets

• Sex and Reproductive Status

1. Patients who are pregnant or breastfeeding or likely to become pregnant

2. Men whose partner is unwilling or unable to avoid pregnancy

1. Patients with a history of non-compliance to CML treatment and monitoring requirements

2. Prisoners or subjects who are involuntarily incarcerated

• Additional Criteria for Patients Eligible to Restart Dasatinib

• Any patient who has lost MMR and is eligible for re-starting dasatinib therapy must not have developed a condition that precludes dasatinib use.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ICON plc

INDUSTRY

Sponsor Role: collaborator

PPD Development, LP

INDUSTRY

Sponsor Role: collaborator

Molecular MD

UNKNOWN

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: collaborator

MultiPharma

UNKNOWN

Sponsor Role: collaborator

Steering Committee

UNKNOWN

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 0006

Duarte, California, United States

Local Institution - 0029

Los Angeles, California, United States

Local Institution - 0001

San Franisco, California, United States

Local Institution - 0013

Chicago, Illinois, United States

Local Institution - 0024

Hackensack, New Jersey, United States

Local Institution - 0028

New York, New York, United States

Local Institution - 0011

Dallas, Texas, United States

Local Institution - 0023

Houston, Texas, United States

Local Institution - 0005

Toronto, Ontario, Canada

Local Institution - 0012

Paris, , France

Local Institution - 0003

Pessac, , France

Local Institution - 0030

Pierre-Bénite, , France

Local Institution - 0002

Vandœuvre-lès-Nancy, , France

Local Institution - 0019

Rostock, Mecklenburg-Vorpommern, Germany

Local Institution - 0026

Aachen, , Germany

Local Institution - 0020

Berlin, , Germany

Local Institution - 0021

Mannheim, , Germany

Local Institution - 0022

Ulm, , Germany

Local Institution - 0025

Catania, , Italy

Local Institution - 0017

Florence, , Italy

Local Institution - 0027

Napoli, , Italy

Local Institution - 0015

Orbassano, , Italy

Local Institution - 0018

Roma, , Italy

Local Institution - 0016

Rome, , Italy

Local Institution - 0014

Oviedo, Principality of Asturias, Spain

Local Institution - 0009

Las Palmas de Gran Canaria, , Spain

Local Institution - 0010

Madrid, , Spain

Local Institution - 0008

Málaga, , Spain

Countries

United States; Canada; France; Germany; Italy; Spain

References

Shah NP, Garcia-Gutierrez V, Jimenez-Velasco A, Larson SM, Saussele S, Rea D, Mahon FX, Levy MY, Gomez-Casares MT, Mauro MJ, Sy O, Martin-Regueira P, Lipton JH. Treatment-free remission after dasatinib in patients with chronic myeloid leukaemia in chronic phase with deep molecular response: Final 5-year analysis of DASFREE. Br J Haematol. 2023 Sep;202(5):942-952. doi: 10.1111/bjh.18883. Epub 2023 May 29.

Reference Type: DERIVED

PMID: 37246588 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.BMSStudyConnect.com

BMS Clinical Trial Patient Recruiting

Other Identifiers

2012-001421-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA180-406

Identifier Type: -

Identifier Source: org_study_id