Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositivePhase 2NCT02689440
Dasatinib and Venetoclax in Treating Patients With Philadelphia Chromosome Positive or BCR-ABL1 Positive Early Chronic Phase Chronic Myelogenous Leukemia
A Phase 2 study testing Dasatinib, Laboratory Biomarker Analysis and Venetoclax in people with Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies how well dasatinib and venetoclax work in treating patients with Philadelphia chromosome positive or BCR-ABL1 positive early chronic phase chronic myelogenous leukemia. Dasatinib and venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia
- What is being tested?
- Dasatinib, Laboratory Biomarker Analysis and Venetoclax
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Feb 2016to 31 Dec 2040
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Ph-positive or BCR-ABL positive CML in early chronic phase CML (i.e., time from diagnosis ≤ 12 months). Except for hydroxyurea and/or 1 to 2 doses of cytarabine patients must have received no or minimal prior therapy, defined as <1 month (30 days) of prior FDA approved TKI.
- Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome has historically been included as a criterion for accelerated phase. However, patients with clonal evolution as the only criterion of accelerated phase have a significantly better prognosis, and when present at diagnosis may not impact the prognosis at all. Thus, patients with clonal evolution and no other criteria for accelerated phase will be eligible for this study.
- Eastern Cooperative Oncology Group (ECOG) performance of 0-2
- Total bilirubin < 1.5 x upper limit normal (ULN) (unless secondary to Gilbert's disease, in which case should be < 2.5x ULN)
- Serum glutamate pyruvate transaminase (SGPT) < 3 x ULN
- Creatinine < 1.5 x ULN
- Patients must sign an informed consent indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital
Who cannot join
- New York Heart Association (NYHA) cardiac class 3-4 heart disease
- Patients meeting the following criteria are not eligible unless cleared by cardiology:
- Uncontrolled angina within 3 months
- Diagnosed or suspected congenital long QT syndrome
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
- Prolonged QTc interval on pre-entry electrocardiogram (> 460 msec)
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- History of significant bleeding disorder unrelated to cancer, including:
- Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
- Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
- Patients with active, uncontrolled psychiatric disorders include: psychosis, major depression, and bipolar disorders
- Subject is known to be positive for human immunodeficiency virus (HIV); (HIV testing is not required)
- Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
- Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
- Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.
- Women of pregnancy potential must practice an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Women must continue birth control for the duration of the trial and at least 3 months after the last dose of study drug.
- Pregnant or breast-feeding women are excluded. All WOCBP must have a negative pregnancy test prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive study drug and must not be enrolled in the study.
- Patients in late chronic phase (i.e., time from diagnosis to treatment > 12 months), accelerated or blast phase are excluded; the definitions of CML phases are as follows:
- Early chronic phase:
- Time from diagnosis to therapy ≤12 months
- Late chronic phase:
- Time from diagnosis to therapy > 12 months
- Blastic phase:
- Presence of 30% blasts or more in the peripheral blood or bone marrow
- Accelerated phase CML:
- Presence of any of the following features:
- Peripheral or marrow blasts 15% or more
- Peripheral or marrow basophils 20% or more
- Thrombocytopenia < 100 x 10^9/L unrelated to therapy
- Documented extramedullary blastic disease outside liver or spleen
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Dasatinib and Venetoclax: A Phase II Study
This phase II trial studies how well dasatinib and venetoclax work in treating patients with Philadelphia chromosome positive or BCR-ABL1 positive early chronic phase chronic myelogenous leukemia. Dasatinib and venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the proportion of patients with previously-untreated chronic phase chronic myeloid leukemia (CML) who achieve major molecular response by 12 months of treatment with dasatinib 50 mg orally daily (first 70 patients) and of dasatinib 50 mg daily in combination with venetoclax 200 mg daily starting after 3 months of dasatinib therapy (after protocol amendment).
SECONDARY OBJECTIVES:
- To estimate the 12 months molecular response (MR)4.5 rate and the cumulative overall rate of MR4.5 (BCR-ABL transcripts [IS] =< 0.01%).
II. To estimate the proportion of patients with MR4.5 at 6-, 12-, 18-, 24-, and 36-months of therapy.
III. To estimate the proportion of patients with sustained MR4.5 of 3 years and more.
IV. To estimate the treatment-free remission rate, time to progression, and overall survival.
- To assess the safety of this combination.
OUTLINE:
Patients receive dasatinib orally (PO) once daily (QD) for 15 years in the absence of disease progression or unacceptable toxicity. After 3 months of dasatinib treatment, patients also receive venetoclax PO QD on days 1-14 of each month for 3 years in the absence of disease progression or unacceptable toxicity (patients enrolled prior to 4/1/2018 receive only dasatinib).
- Conditions
- Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia
- Being tested
- Dasatinib, Laboratory Biomarker Analysis, Venetoclax
- Medical subject headings
- Leukemia, Myeloid, Chronic-Phase, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (dasatinib, venetoclax) | Experimental | Patients receive dasatinib PO QD for 15 years in the absence of disease progression or unacceptable toxicity. After 3 months of dasatinib treatment, patients also receive venetoclax PO QD on days 1-14 of each month for 3 years in the absence of disease progression or unacceptable toxicity (patients enrolled prior to 4/1/2018 receive only dasatinib). Receives: Drug: Dasatinib; Other: Laboratory Biomarker Analysis; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major molecular response (MMR) defined as BCR-ABL transcripts (IS) =< 0.1%
MMR estimates will be presented with 95% credible intervals. MMR and patient and clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test.
Measured: Up to 12 months
Secondary outcomes (4)
Complete cytogenetic response (CCR) defined as 0% Ph-positive metaphases, or fluorescence in situ hybridization =< 2%, or BCR-ABL transcripts (IS) =< 1%
CCR estimates will be presented with 95% credible intervals.
Measured: At 6 months
Incidence of toxicities, defined as grade 3 or higher pleural effusion
Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median and range (i.e., duration of hematologic, cytogenetic and molecular response to the drug).
Measured: Up to 3 years
Time to progression
Estimated using the Kaplan-Meier method. The two-sided log-rank test will be used to assess the differences of time to events between groups.
Measured: Up to 3 years
Overall survival
Estimated using the Kaplan-Meier method. The two-sided log-rank test will be used to assess the differences of time to events between groups.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2016 (estimated)
- Study start19 Feb 2016
- Primary completion31 Dec 2040 (estimated)
- Study completion31 Dec 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Elias Jabbour, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02689440
- Sponsor's protocol ID
- 2015-1040
- Other IDs
- NCI-2016-00362, 2015-1040
- Status last verified
- Sep 2026
- First submitted
- 19 Feb 2016
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Gener-Ricos G, Haddad FG, Sasaki K, Issa GC, Skinner J, Masarova L, Borthakur G, Alvarado Y, Garcia-Manero G, Jabbour E, Kantarjian H. Low-Dose Dasatinib (50 mg Daily) Frontline Therapy in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: 5-Year Follow-Up Results. Clin Lymphoma Myeloma Leuk. 2023 Oct;23(10):742-748. doi: 10.1016/j.clml.2023.05.009. Epub 2023 May 23.
PubMed 37308342Naqvi K, Jabbour E, Skinner J, Anderson K, Dellasala S, Yilmaz M, Ferrajoli A, Bose P, Thompson P, Alvarado Y, Jain N, Takahashi K, Burger J, Estrov Z, Borthakur G, Pemmaraju N, Paul S, Cortes J, Kantarjian HM. Long-term follow-up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic-phase chronic myeloid leukemia. Cancer. 2020 Jan 1;126(1):67-75. doi: 10.1002/cncr.32504. Epub 2019 Sep 25.
PubMed 31553487Naqvi K, Jabbour E, Skinner J, Yilmaz M, Ferrajoli A, Bose P, Thompson P, Alvarado Y, Jain N, Takahashi K, Burger J, Estrov Z, Borthakur G, Pemmaraju N, Paul S, Cortes J, Kantarjian HM. Early results of lower dose dasatinib (50 mg daily) as frontline therapy for newly diagnosed chronic-phase chronic myeloid leukemia. Cancer. 2018 Jul 1;124(13):2740-2747. doi: 10.1002/cncr.31357. Epub 2018 May 3.
PubMed 29723397