Clinical trial NCT01850004: Open-Label Study Evaluating Dasatinib Therapy Discontinuation in Patients With Chronic Phase Chronic Myeloid Leukemia With Stable Complete Molecular Response
Official title: Open-Label Single Arm Phase 2 Study Evaluating Dasatinib Therapy Discontinuation In Patients With Chronic Phase Chronic Myeloid Leukemia (CP-CML) With Stable Complete Molecular Response (CMR) DASFREE
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Phase Chronic Myeloid Leukemia
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: ICON plc
name: PPD Development, LP
name: Molecular MD
name: European Organisation for Research and Treatment of Cancer - EORTC
name: MultiPharma
name: Steering Committee
First posted: 2013-05-09
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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

Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

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
* Other Exclusion Criteria

  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.

Other protocol defined inclusion/exclusion criteria could apply

Primary outcomes:
measure: Major Molecular Response (MMR) Rate
timeFrame: At 12 months after Dasatinib discontinuation (assessed up to approximately June 4, 2018)
Secondary outcomes:
measure: Event-Free Survival (EFS) Rate
timeFrame: From 12 months after Dasatinib treatment discontinuation to every 12 months thereafter (up to approximately 60 months)
measure: Relapse-Free Survival (RFS) Rate
timeFrame: From 12 months after Dasatinib treatment discontinuation to every 6 months thereafter (up to approximately 60 months)
measure: Progression Free Survival (PFS) Rate
timeFrame: From 12 months after Dasatinib treatment discontinuation to every 6 months thereafter (up to approximately 60 months)
measure: Number of Participants Who Experience Intermittent Loss of Complete Molecular Response (CMR) (MR4.5) But no Loss of Major Molecular Response (MMR)
timeFrame: 60 months after last dose
measure: Number of Participants Who Did Not Experience Loss of Complete Molecular Response (CMR) (MR4.5) and Major Molecular Response (MMR)
timeFrame: From 12 months after Dasatinib treatment discontinuation to 5 years after the first visit of the last enrolled participant (up to approximately 82 months)
measure: Time to Transformation to Accelerated Phase/Blast Crisis (AP/BC)
timeFrame: From 12 months after Dasatinib treatment discontinuation to 5 years after the first visit of the last enrolled participant (up to approximately 82 months)
measure: Overall Survival (OS)
timeFrame: From 12 months after Dasatinib treatment discontinuation to the date of death or last known alive date (up to approximately 82 months)
measure: Progression Free Survival
timeFrame: From treatment discontinuation to the date of progression or death due to any cause, whichever occurs first (up to 82 months)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Local Institution - 0006
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0029
state: California
city: San Franisco
country: United States
facility: Local Institution - 0001
state: California
city: Chicago
country: United States
facility: Local Institution - 0013
state: Illinois
city: Hackensack
country: United States
facility: Local Institution - 0024
state: New Jersey
city: New York
country: United States
facility: Local Institution - 0028
state: New York
city: Dallas
country: United States
facility: Local Institution - 0011
state: Texas
city: Houston
country: United States
facility: Local Institution - 0023
state: Texas
city: Toronto
country: Canada
facility: Local Institution - 0005
state: Ontario
city: Paris
country: France
facility: Local Institution - 0012
city: Pessac
country: France
facility: Local Institution - 0003
city: Pierre Benite Cedex
country: France
facility: Local Institution - 0030
city: Vandoeuvre-les-Nancy CEDEX
country: France
facility: Local Institution - 0002
city: Rostock
country: Germany
facility: Local Institution - 0019
state: Mecklenburg Vorpommern
city: Aachen
country: Germany
facility: Local Institution - 0026
city: Berlin
country: Germany
facility: Local Institution - 0020
city: Mannheim
country: Germany
facility: Local Institution - 0021
city: Ulm
country: Germany
facility: Local Institution - 0022
city: Catania
country: Italy
facility: Local Institution - 0025
city: Firenze
country: Italy
facility: Local Institution - 0017
city: Napoli
country: Italy
facility: Local Institution - 0027
city: Orbassano
country: Italy
facility: Local Institution - 0015
city: Roma
country: Italy
facility: Local Institution - 0018
city: Rome
country: Italy
facility: Local Institution - 0016
city: Oviedo
country: Spain
facility: Local Institution - 0014
state: Asturias
city: Las Palmas de Gran Canaria
country: Spain
facility: Local Institution - 0009
city: Madrid
country: Spain
facility: Local Institution - 0010
city: Malaga
country: Spain
facility: Local Institution - 0008
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: