A Phase 2 interventional study of Cytarabine and Dasatinib in Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome and Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11, sponsored by National Cancer Institute (NCI). Completed at 65 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-03-01.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
This phase II trial studies the side effects and how well giving combination chemotherapy together with dasatinib works in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as daunorubicin hydrochloride and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with dasatinib may kill more cancer cells.
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of dasatinib 100 mg/day given after intensive induction (daunorubicin hydrochloride [daunorubicin]/cytarabine), and consolidation chemotherapy (high-dose cytarabine) and as single agent in maintenance therapy to newly diagnosed patients with core binding factor acute myeloid leukemia (AML).
II. 30-day survival rate during induction (the lack of early/hypoplastic death).
III. The absence of pleural or pericardial effusion, and absence of liver toxicity that exceeds grade 2.
SECONDARY OBJECTIVES:
I. To assess clinical outcomes such as event-free survival (EFS), complete response (CR) rate, cumulative incidence of relapse (CIR), cumulative incidence of death (CID), disease-free survival (DFS), and overall survival (OS).
II. To describe the frequency and severity of adverse events of patients treated on this study during induction, consolidation, and continuation therapy.
III. To describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood cell (WBC) count and hemogram, and performance status on clinical outcomes.
OUTLINE:
INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride intravenously (IV) on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib orally (PO) once daily (QD) on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and patients with non-responsive disease on day 21 (bone marrow cellularity >= 20 % and leukemia blasts >= 5%) receive a second course of induction therapy.
INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO once a day on days 6-19. Patients achieving complete response receive consolidation therapy.
CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO QD on days 6-26 or 7-27. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy.
CONTINUATION THERAPY: Patients receive dasatinib PO on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then every year for up to 10 years from study entry.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 61 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
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Inclusion Criteria:
No prior chemotherapy for leukemia or myelodysplasia with the following exceptions:
INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib PO QD on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and patients with non-responsive disease on day 21 (bone marrow cellularity \>= 20% and leukemia blasts \>= 5%) receive a second course of induction therapy. INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO QD on days 6-19. Patients achieving complete response receive consolidation therapy. CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO QD on days 6-26 or 7-27. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy.
Drug: Cytarabine · Drug: Dasatinib · Drug: Daunorubicin Hydrochloride · Other: Laboratory Biomarker Analysis
Given IV
Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453
Given PO
Also known as: BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel
Given IV
Also known as: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin Hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilem
Correlative studies
30 Day Survival Rate
Percentage of participants who were alive 30 days after starting induction treatment.
Time frame: 30 days
Event-free Survival
Event free survival (EFS) is defined as the time from registration to failure to achieve complete remission (CR), relapse after CR is attained or death, whichever comes first. The 1 year EFS rate with 95% CI was estimated using the Kaplan-Meier method, Complete remission (CR) is defined as: disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x 10\^9/L and platelet count \> 100 x 10\^9/L, and normal bone marrow differential (\< 5% blasts).
Time frame: 1 year
Complete Response Rate
Percentage of participants who achieve a CR. Complete remission (CR) is defined as: disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x 10\^9/L and platelet count \> 100 x 10\^9/L, and normal bone marrow differential (\< 5% blasts).
Time frame: 60 months
Cumulative Incidence of Relapse
Time frame: 60 months
Cumulative Incidence of Death
Time frame: 36 months
Disease-free Survival
Disease free survival (DFS) is defined as the time from achievement of CR to relapse or death, whichever comes first. The 3 year DFS rate with 95% CI was estimated using the Kaplan-Meier method.
Time frame: 3 years
Overall Survival
Overall survival (OS) is defined as time from registration to death. The 3 year OS rate with 95% CI was estimated using the Kaplan-Meier method.
Time frame: 3 years
Between April 2011 and January 2013, 61 participants were recruited.
| Milestone | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| Started | 61 |
| Completed | 3 |
| Not completed | 58 |
| Withdrew: Continues active treatment | 31 |
| Withdrew: Adverse event | 7 |
| Withdrew: Death | 4 |
| Withdrew: Relapse/progression | 2 |
| Withdrew: Withdrawal by subject | 7 |
| Withdrew: Non-protocol treatment | 4 |
| Withdrew: Investigator/patient decision | 3 |
Percentage of participants who were alive 30 days after starting induction treatment.
| percentage of participants | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| 30 Day Survival Rate | 97 (89 to 99.6) |
Event free survival (EFS) is defined as the time from registration to failure to achieve complete remission (CR), relapse after CR is attained or death, whichever comes first. The 1 year EFS rate with 95% CI was estimated using the Kaplan-Meier method, Complete remission (CR) is defined as: disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x 10\^9/L and platelet count \> 100 x 10\^9/L, and normal bone marrow differential (\< 5% blasts).
| percentage of patients | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| Event-free Survival | 83 (70.7 to 90.5) |
Percentage of participants who achieve a CR. Complete remission (CR) is defined as: disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x 10\^9/L and platelet count \> 100 x 10\^9/L, and normal bone marrow differential (\< 5% blasts).
| percentage of patients | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| Complete Response Rate | 90 (80 to 96) |
| Participants | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| Cumulative Incidence of Relapse | 10 |
| Participants | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| Cumulative Incidence of Death | 15 |
Disease free survival (DFS) is defined as the time from achievement of CR to relapse or death, whichever comes first. The 3 year DFS rate with 95% CI was estimated using the Kaplan-Meier method.
| percentage of patients | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| Disease-free Survival | 75 (63 to 89) |
Overall survival (OS) is defined as time from registration to death. The 3 year OS rate with 95% CI was estimated using the Kaplan-Meier method.
| percentage of patients | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| Overall Survival | 77 (66 to 89) |
Collected over 3 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) | 15/61 (24.6%) | 27/61 (44.3%) | 61/61 (100%) |
| Event | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| Platelet count decreasedInvestigations | 27/61 |
| AnemiaBlood and lymphatic system disorders | 26/61 |
| Neutrophil count decreasedInvestigations | 26/61 |
| FatigueGeneral disorders | 22/61 |
| HypoalbuminemiaMetabolism and nutrition disorders | 21/61 |
| NauseaGastrointestinal disorders | 20/61 |
| HyperglycemiaMetabolism and nutrition disorders | 19/61 |
| Febrile neutropeniaBlood and lymphatic system disorders | 18/61 |
| Lymphocyte count decreasedInvestigations | 18/61 |
| White blood cell decreasedInvestigations | 18/61 |
| Event | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| AnemiaBlood and lymphatic system disorders | 58/61 |
| Neutrophil count decreasedInvestigations | 51/61 |
| Platelet count decreasedInvestigations | 51/61 |
| Febrile neutropeniaBlood and lymphatic system disorders | 47/61 |
| NauseaGastrointestinal disorders | 47/61 |
| FatigueGeneral disorders | 47/61 |
| DiarrheaGastrointestinal disorders | 44/61 |
| Alanine aminotransferase increasedInvestigations | 41/61 |
| White blood cell decreasedInvestigations | 40/61 |
| HyperglycemiaMetabolism and nutrition disorders | 40/61 |
| Age, Continuous(years) | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| Median | 51 (19.8 to 85) |
| Sex: Female, Male(Participants) | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| Female | 30 |
| Male | 31 |
| Ethnicity (NIH/OMB)(Participants) | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 54 |
| Unknown or Not Reported | 7 |
| Race (NIH/OMB)(Participants) | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 1 |
| Black or African American | 5 |
| White | 46 |
| More than one race | 0 |
| Unknown or Not Reported | 8 |
| Region of Enrollment(participants) | Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) |
|---|---|
| United States | 61 |
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