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

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ClinicalTrials.gov Identifier: NCT01850004
Recruitment Status : Active, not recruiting
First Posted : May 9, 2013
Results First Posted : November 2, 2018
Last Update Posted : November 2, 2018
Sponsor:
Collaborators:
ICON plc
PPD
Molecular MD
European Organisation for Research and Treatment of Cancer - EORTC
MultiPharma
Steering Committee
Information provided by (Responsible Party):
Bristol-Myers Squibb

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.

Condition or disease Intervention/treatment Phase
Chronic Phase Chronic Myeloid Leukemia Drug: Dasatinib Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : October 23, 2013
Actual Primary Completion Date : September 20, 2017
Estimated Study Completion Date : October 10, 2021


Arm Intervention/treatment
Experimental: Dasatinib
Dasatinib 50, 80, 100, 140, 180 mg tablets by mouth, once daily, up to 60 months
Drug: Dasatinib
Other Name: Sprycel




Primary Outcome Measures :
  1. Major Molecular Response (MMR) Rate [ Time Frame: At 12 months after Dasatinib discontinuation (assessed up to approximately June 4, 2018) ]
    Major Molecular Response (MMR) rate at 12 months is the percentage of participants who maintain MMR (BCR-ABL transcripts < 0.1% on the International Scale [IS]) at 12 months after Dasatinib discontinuation without restarting Dasatinib


Secondary Outcome Measures :
  1. Event-free Survival (EFS) Rate After Dasatinib Discontinuation [ Time Frame: At 12 months ]
    EFS was defined as the time from the date of dasatinib treatment discontinuation to the date of loss of MMR.

  2. Relapse-free Survival (RFS) After Dasatinib Discontinuation [ Time Frame: At 6,12,18, 24 months and every 6 months thereafter up to 5 years ]
    Relapse is defined as any of the following events while a subject is on study: the loss of MMR, loss of Complete Cytogenetic Response (CCyR), loss of Complete Hematologic Response (CHR) or progression to advanced/blastic phase. RFS is defined as the time from Dasatinib treatment discontinuation to the date of relapse. Subjects who did not relapse were censored on the date of their last molecular assessment.

  3. Progression Free Survival (PFS) Rate [ Time Frame: From Dasatinib treatment discontinuation up to 5 years ]
    Progression is defined as Transformation to Accelerated Phase or Blast Crisis (AP/BC) Accelerated Phase (AP) Blasts in PB or BM 15-29%; Blast + promyelocytes >= 30% with blasts < 30% or ACA in Ph+ cells (clonal progression), or basophils in blood >= 20%,or platelets < 100 x 109 /L unrelated to therapy Blastic Phase or Crisis (BP/BC) Blasts in PB or BM >= 30%, or extramedullary blast cell involvement (with the exception of spleen and liver)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01850004


Locations
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United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
Ucsf-Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, Illinois
Northwestern University, Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, New Jersey
John Theurer Cancer Center, Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center
New York, New York, United States, 10032
United States, Texas
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas, Texas, United States, 75246
MD Anderson Cancer Center Clinic
Houston, Texas, United States, 77030-4000
Canada, Ontario
Local Institution
Toronto, Ontario, Canada, M5G 2M9
France
Local Institution
Paris, France, 75010
Local Institution
Pessac, France, 33604
Local Institution
Pierre Benite Cedex, France, 69495
Local Institution
Vandoeuvre-les-Nancy Cedex, France, 54511
Germany
Local Institution
Aachen, Germany, D-52074
Local Institution
Berlin, Germany, 13353
Local Institution
Mannheim, Germany, 68167
Local Institution
Rostock, Germany, 18057
Local Institution
Ulm, Germany, 89081
Italy
Local Institution
Catania, Italy, 95123
Local Institution
Firenze, Italy, 50134
Local Institution
Napoli, Italy, 80131
Local Institution
Orbassano, Italy, 10043
Local Institution
Roma, Italy, 00144
Local Institution
Roma, Italy, 00161
Spain
Local Institution
Las Palmas de Gran Canaria, Spain, 35010
Local Institution
Madrid, Spain, 28034
Local Institution
Malaga, Spain, 29010
Local Institution
Oviedo, Spain, 33011
Sponsors and Collaborators
Bristol-Myers Squibb
ICON plc
PPD
Molecular MD
European Organisation for Research and Treatment of Cancer - EORTC
MultiPharma
Steering Committee
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] July 24, 2017
Statistical Analysis Plan  [PDF] July 13, 2018


Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01850004     History of Changes
Other Study ID Numbers: CA180-406
2012-001421-27 ( EudraCT Number )
First Posted: May 9, 2013    Key Record Dates
Results First Posted: November 2, 2018
Last Update Posted: November 2, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action