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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Mole

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

Current Primary Outcome: MMR rate at 12 months [ Time Frame: At 12 months after Dasatinib discontinuation ]

Major Molecular Response (MMR) rate at 12 months is the proportion of subjects who maintain MMR at 12 months after Dasatinib discontinuation without re-starting Dasatinib treatment in the enrolled subjects in the study


Original Primary Outcome:

  • MMR rate measured by the proportion of enrolled subjects who maintain MMR 12 months after Dasatinib discontinuation compared with the enrolled subjects in the study [ Time Frame: Monthly once up to first year ]
    Major Molecular Response (MMR) is defined as BCR-ABL transcripts <0.1% on International Scale, at 12 month after Dasatinib discontinuation in patients who have maintained MMR without re-starting Dasatinib
  • MMR rate measured by the proportion of enrolled subjects who maintain MMR 12 months after Dasatinib discontinuation compared with the enrolled subjects in the study [ Time Frame: Every 3 months in years 2 to 5 ]


Current Secondary Outcome:

  • Event-free survival (EFS) after Dasatinib discontinuation [ Time Frame: At 12 months after Dasatinib discontinuation ]
    EFS is defined as survival with no molecular relapse, including no loss of MMR
  • 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, Complete Cytogenetic Response (CCyR), 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
  • Assessment of BCR-ABL kinetics for subjects who experience loss of Complete Molecular Response (CMR) but not MMR [ Time Frame: Monthly in the first year and every 3 months thereafter up to 5 years ]
  • Assessment of BCR-ABL kinetics in subjects in CMR or less with measurable levels [ Time Frame: Monthly in the first year and every 3 months thereafter up to 5 years ]
  • Rate of transformation to AP/BC [ Time Frame: Up to 5 years or death date ]

    Accelerated Phase (AP) is defined as Blasts in Peripheral Blood (PB) or Bone Marrow (BM) 15-29%; Blast+promyelocytes ≥30% with blasts < 30% or Additional Chromosomal Abnormalities (ACA) in Ph+ cells (clonal progression), or basophils in blood ≥ 20% or platelets <100 x 10(9)/L unrelated to therapy

    Blastic Phase or Crisis (BP/BC) is defined as Blasts in PB or BM ≥30%, or extramedullary blast cell involvement (with the exception of spleen and liver)

  • Progression Free Survival (PFS) [ Time Frame: Up to 5 years or death date ]
    Progression-free survival (PFS) is defined as overall survival plus the additional events progression to accelerated phase or blast crisis
  • Overall survival (OS) [ Time Frame: Up to 5 years or death date ]
    Overall survival (OS) is defined as the time between first dose date and death date


Original Secondary Outcome:

  • Event-free survival (EFS) after Dasatinib discontinuation [ Time Frame: At 12 months after Dasatinib discontinuation ]
    EFS is defined as survival with no molecular relapse, including no loss of MMR
  • Relapse-free survival (RFS) after Dasatinib discontinuation [ Time Frame: At 6, 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, Complete Cytogenetic Response (CCyR), Complete Hematologic Response (CHR) or progression to advanced/blastic phase or has a serious drug toxicity. RFS is defined as the time from Dasatinib treatment discontinuation to the date of relapse
  • Assessment of BCR-ABL kinetics for subjects who experience loss of Complete Molecular Response (CMR) but not MMR [ Time Frame: Monthly in the first year and every 3 months thereafter up to 5 years ]
  • Assessment of BCR-ABL kinetics in subjects in CMR with measurable levels [ Time Frame: Monthly in the first year and every 3 months thereafter up to 5 years ]
  • Rate of transformation to AP/BC and OS [ Time Frame: Up to 5 years or death date ]

    Accelerated Phase (AP) is defined as Blasts in Peripheral Blood (PB) or Bone Marrow (BM) 15-29%; Blast+promyelocytes ≥50% or ACA in Ph+ cells (clonal progression), or platelets <100 x 109/L unrelated to therapy

    Blastic Phase or Crisis (BP/BC) is defined as Blasts in PB or BM ≥30%, or extramedullary blast cell involvement (with the exception of spleen and liver)

    Overall survival (OS) is defined as the time between first dose date and death date



Information By: Bristol-Myers Squibb

Dates:
Date Received: May 8, 2013
Date Started: October 2013
Date Completion: November 2021
Last Updated: April 17, 2017
Last Verified: November 2016