Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myeloid, Chronic-Phase

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Dasatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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

Bristol-Myers Squibb

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

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

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

Event-free survival (EFS) rate is defined as the percentage of surviving participants with no loss of Major Molecular Response (MMR) at the specified timepoints after dasatinib discontinuation. MMR is defined as BCR-ABL transcripts \< 0.1% IS. Loss of MMR is defined per the European LeukemiaNet (ELN) definition of progression. 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 10\^9 /L unrelated to therapy

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

The date of progression is defined as the date any of the above criteria is first met. Participants who have not progressed will be censored on the date of last examination.

RFS is the percentage of participants who did not relapse at the specified timepoints. Participants who did not relapse were censored on the date of their last molecular assessment. Relapse is defined as any of the following events while on study: the loss of Major Molecular Response (MMR), loss of Complete Cytogenetic Response (CCyR), loss of Complete Hematologic Response (CHR) or progression to advanced/blastic phase.

MMR is defined as BCR-ABL transcripts \< 0.1% IS. Cytogenetic response (CyR) is based on the prevalence of Ph+ cells in metaphase from bone marrow (BM) sample based on evaluation of at least 20 metaphases. CCyR is defined as 0% Ph+ cells in metaphase in BM. CHR is obtained when all the following criteria are met in peripheral blood (PB) sampling: white blood cell ≤10,000/mm3; Platelets \< 450,000/mm3; PB basophils \<5%; No blasts or promyelocytes in PB; \<5% myelocytes plus metamyelocytes in PB; No extramedullary involvement (including no hepatomegaly or splenomegaly).

Progression free survival (PFS) is defined as the percentage of participants who experienced death (due to any cause) or accelerated phase, or blast crisis. Participants who neither progress nor die will be censored on the date of their last molecular assessment. 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)

The number of participants who did not lose major molecular response (MMR) 60 months after discontinuing study treatment who were in MR4.5 at the time of discontinuation and lost MR4.5. Molecular response will be assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (Q-PCR). MMR is defined as BCR-ABL transcripts \< 0.1% Internal Standard (IS). CMR (MR4.5) defined as ≤ 0.0032% (IS) or ≥ 4.5 log reduction of BCR-ABL transcript levels molecular response.

Assessment of BCR-ABL kinetics in patients who are in CMR (MR4.5) or less when transcript levels are still measurable. CMR (MR4.5) defined as ≤ 0.0032% (IS) or ≥ 4.5 log reduction of BCR-ABL transcript levels molecular response.

Time to Transformation to AP/BC is defined as the rate at which participants experienced transformation to accelerated phase/blast crisis (AP/BC) since discontinuation. Participants who did not develop to AP, late phase, or BC phase were censored on their last molecular measurement date.

Overall survival (OS) is defined as the time from dasatinib treatment discontinuation to the date of death (due to any cause) or last known alive date. Participants who do not die will be censored on their last known alive date.

Progression-free survival (PFS) is defined as the time from treatment discontinuation to the date of progression or death (due to any cause), whichever occurs first. Participants who neither progress nor die will be censored on the date of their last molecular assessment.

ICON plc

Molecular MD

European Organisation for Research and Treatment of Cancer - EORTC

MultiPharma

Steering Committee

The number at Risk for All-Cause Mortality represents all enrolled Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication during re-treatment.

Prior to study entry participants received dasatinib as treatment for a minimum of 2 years. Upon enrollment dasatinib will be discontinued. Dasatinib will be restarted if major molecular response is lost during the off-treatment period at the dose level received before study entry. The participant will remain on treatment for the duration of the study.

Total

Age, Continuous

Sex: Female, Male

White

Black/African American

Asian

Other

Race/Ethnicity, Customized

Bristol-Myers Squibb Study Director

Major Molecular Response (MMR) Rate

At 12 months

At 24 months

At 36 months

At 48 months

At 60 months

Event-Free Survival (EFS) Rate

At 6 Months

At 12 Months

At 18 Months

At 30 months

At 42 months

At 54 months

Relapse-Free Survival (RFS) Rate

At 6 months

At 18 months

Progression Free Survival (PFS) Rate

Participants with no loss of major molecular response (MMR)

Number of Participants Who Experience Intermittent Loss of Complete Molecular Response (CMR) (MR4.5) But no Loss of Major Molecular Response (MMR)

Number of Participants Who Did Not Experience Loss of Complete Molecular Response (CMR) (MR4.5) and Major Molecular Response (MMR)

Time to Transformation to Accelerated Phase/Blast Crisis (AP/BC)

Overall Survival (OS)

Progression Free Survival

Overall Study

Spots Global Cancer Trial Database for Open-Label Study Evaluating Dasatinib Therapy Discontinuation in Patients With Chronic Phase Chronic Myeloid Leukemia With Stable Complete Molecular Response

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial