Dasatinib and Venetoclax in Treating Patients With Philadelphia Chromosome Positive or BCR-ABL1 Positive Early Chronic Phase Chronic Myelogenous Leukemia

NCT02689440 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2015-1040NCI-2016-00362
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia

Outcome Measures

Primary Outcomes (1)

• 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.

  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%

  At 6 months

• Incidence of toxicities, defined as grade 3 or higher pleural effusion

  Up to 3 years

• Time to progression

  Up to 3 years

• Overall survival

  Up to 3 years

Study Arms (1)

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).

Drug: Dasatinib; Other: Laboratory Biomarker Analysis; Drug: Venetoclax

Interventions

Dasatinib DRUG

Given PO

Also known as: BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel

Treatment (dasatinib, venetoclax)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (dasatinib, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (dasatinib, venetoclax)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

• 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.

  PMID: 37308342 DERIVED

• Naqvi 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.

  PMID: 31553487 DERIVED

• Naqvi 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.

  PMID: 29723397 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Dasatinib; venetoclax

Condition Hierarchy (Ancestors)

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

Study Officials

• Elias Jabbour, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 19, 2016
• First Posted: February 24, 2016
• Study Start: February 19, 2016
• Primary Completion (Estimated): December 31, 2040
• Study Completion (Estimated): December 31, 2040
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)