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

NCT01850004 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CA180-4062012-001421-27
• Study Type: interventional
• Target: 84
• Locations: 6 countries
• Sites: 28

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.

Conditions

Chronic Phase Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Major Molecular Response (MMR) Rate

  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

  At 12 months after Dasatinib discontinuation (assessed up to approximately June 4, 2018)

Secondary Outcomes (8)

• Event-Free Survival (EFS) Rate

  From 12 months after Dasatinib treatment discontinuation to every 12 months thereafter (up to approximately 60 months)

• Relapse-Free Survival (RFS) Rate

  From 12 months after Dasatinib treatment discontinuation to every 6 months thereafter (up to approximately 60 months)

• Progression Free Survival (PFS) Rate

  From 12 months after Dasatinib treatment discontinuation to every 6 months thereafter (up to approximately 60 months)

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

  60 months after last dose

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

  From 12 months after Dasatinib treatment discontinuation to 5 years after the first visit of the last enrolled participant (up to approximately 82 months)

Study Arms (1)

Dasatinib

EXPERIMENTAL

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

Drug: Dasatinib

Interventions

Dasatinib DRUG

Also known as: Sprycel

Dasatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Written Informed Consent
• Target Population
• 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.
• 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.
• 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.
• Eastern Co-Operative Group (ECOG) Performance Status (PS) of 0-1
• Age and Reproductive Status
• Men and women, ages ≥18
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the restart of study drug
• Women must not be breastfeeding
• 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
• 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

You may not qualify if:

• Target Disease Exceptions
• 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.
• Patients who have previously undergone hematopoietic stem cell transplantation (SCT) or who are scheduled for SCT
• Previous diagnosis of CML accelerated phase or blast crisis
• Medical History and Concurrent Diseases
• 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
• 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.
• Uncontrolled or significant cardiovascular disease
• 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.
• History of significant bleeding disorder unrelated to CML
• Allergies and Adverse Drug Reaction

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• ICON plc: collaborator
• PPD Development, LP: collaborator
• Molecular MD: collaborator
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator
• MultiPharma: collaborator
• Steering Committee: collaborator

Study Sites (28)

Local Institution - 0006

Duarte, California, 91010, United States

Location

Local Institution - 0029

Los Angeles, California, 90095, United States

Location

Local Institution - 0001

San Franisco, California, 94143, United States

Location

Local Institution - 0013

Chicago, Illinois, 60611, United States

Location

Local Institution - 0024

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0028

New York, New York, 10032, United States

Location

Local Institution - 0011

Dallas, Texas, 75246, United States

Location

Local Institution - 0023

Houston, Texas, 77030-4000, United States

Location

Local Institution - 0005

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 0012

Paris, 75475, France

Location

Local Institution - 0003

Pessac, 33604, France

Location

Local Institution - 0030

Pierre-Bénite, 69495, France

Location

Local Institution - 0002

Vandœuvre-lès-Nancy, 54511, France

Location

Local Institution - 0019

Rostock, Mecklenburg-Vorpommern, 18057, Germany

Location

Local Institution - 0026

Aachen, D-52074, Germany

Location

Local Institution - 0020

Berlin, 13353, Germany

Location

Local Institution - 0021

Mannheim, 68167, Germany

Location

Local Institution - 0022

Ulm, 89081, Germany

Location

Local Institution - 0025

Catania, 95123, Italy

Location

Local Institution - 0017

Florence, 50134, Italy

Location

Local Institution - 0027

Napoli, 80131, Italy

Location

Local Institution - 0015

Orbassano, 10143, Italy

Location

Local Institution - 0018

Roma, 00144, Italy

Location

Local Institution - 0016

Rome, 00161, Italy

Location

Local Institution - 0014

Oviedo, Principality of Asturias, 33011, Spain

Location

Local Institution - 0009

Las Palmas de Gran Canaria, 35010, Spain

Location

Local Institution - 0010

Madrid, 28034, Spain

Location

Local Institution - 0008

Málaga, 29010, Spain

Location

Related Publications (1)

• Shah NP, Garcia-Gutierrez V, Jimenez-Velasco A, Larson SM, Saussele S, Rea D, Mahon FX, Levy MY, Gomez-Casares MT, Mauro MJ, Sy O, Martin-Regueira P, Lipton JH. Treatment-free remission after dasatinib in patients with chronic myeloid leukaemia in chronic phase with deep molecular response: Final 5-year analysis of DASFREE. Br J Haematol. 2023 Sep;202(5):942-952. doi: 10.1111/bjh.18883. Epub 2023 May 29.

  PMID: 37246588 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 9, 2013
• Study Start: January 22, 2014
• Primary Completion: September 20, 2017
• Study Completion: October 8, 2021
• Last Updated: November 3, 2022
• Results First Posted: November 2, 2018

Record last verified: 2022-10

Locations

DE (5); ES (4); IT (6); US (8); FR (4); CA (1)