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

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

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.

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

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