First-line Dasatinib Plus Conventional Chemotherapy in Adults With Newly Diagnosed Ph-Positive ALL - Full Text View

Purpose

The main aim of the present study is to evaluate the clinical efficacy of first-line dasatinib plus conventional chemotherapy for newly diagnosed Ph-positive acute lymphoblastic leukemia. In this study, the investigators will analyze the clinical outcomes for entire patient population as well as those for transplants, respectively. In addition, the results of this study will be compared to those of the investigators current study (imatinib plus conventional chemotherapy). The safety of this treatment will also be studied.

Condition	Intervention	Phase
Acute Lymphoblastic Leukemia	Drug: Dasatinib Drug: Cyclophosphamide Drug: Vincristine Drug: Daunorubicin Drug: Dexamethasone Drug: Cytarabine Drug: Mitoxantrone	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 2 Multicenter Study of First-line Dasatinib Plus Conventional Chemotherapy in Adults With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Resource links provided by NLM:

Further study details as provided by The Catholic University of Korea:

Primary Outcome Measures:

To determine the clinical efficacy of dasatinib plus conventional chemotherapy for newly diagnosed Ph-positive ALL in terms of major molecular response rate [ Time Frame: by the second 4-week dasatinib therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate the long-term clinical outcomes (including transplant outcomes) in terms of treatment toxicity, relapse, disease-free survival, and overall survival [ Time Frame: at 2 years after transplantation (for all transplants); at 2 years after starting dasatinib maintenance (for all non-transplants) ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	51
Study Start Date:	March 2010
Estimated Study Completion Date:	September 2014
Estimated Primary Completion Date:	March 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Modified Hyper-CVAD + Dasatinib Dasatinib: 100 mg once daily, PO, for 4 weeks Cyclophosphamide: 300 mg/m2, IV, every 12 hours, days 1~3 Vincristine: 1.4 mg/m2/day (maximum 2 mg/day), IV, days 4 & 11 Daunorubicin: 45 mg/m2/day, IV, days 4 & 11 Dexamethasone: 40 mg/day, IV, days 1~4 & days 11~14 Cytarabine: 2 g/m2, IV, every 12 hours, days 1~5 Mitoxantrone: 12 mg/m2/day, IV, days 1~2	Drug: Dasatinib After the completion of each induction and consolidation chemotherapy with recovery of leukocyte and platelet counts, dasatinib will be given as an alternative manner: 100 mg by mouth once daily for 4 weeks Other Name: Sprycel Drug: Cyclophosphamide 300 mg/m2, IV for 2 hours, every 12 hours x 6 doses, days 1-3 Other Name: Endoxan Drug: Vincristine 1.4 mg/m2/day (maximum 2 mg/day), IV for 30 minutes, days 4 & 11 Other Name: Vincristine sulfate Drug: Daunorubicin 45 mg/m2/day, IV for 1 hour, days 4 & 11 Other Name: Cerubidine Drug: Dexamethasone 40 mg/day, IV push, days 1-4 & days 11-14 Other Name: Dexamethasone disodium phosphate Drug: Cytarabine 2 g/m2, IV for 3 hours, every 12 hours x 10 doses, days 1-5 Other Name: Cytosar U Drug: Mitoxantrone 12 mg/m2/day, IV for 30 minutes, days 1-2 Other Name: Mitrone

Arms

Assigned Interventions

Experimental: Modified Hyper-CVAD + Dasatinib

Dasatinib: 100 mg once daily, PO, for 4 weeks Cyclophosphamide: 300 mg/m2, IV, every 12 hours, days 1~3 Vincristine: 1.4 mg/m2/day (maximum 2 mg/day), IV, days 4 & 11 Daunorubicin: 45 mg/m2/day, IV, days 4 & 11 Dexamethasone: 40 mg/day, IV, days 1~4 & days 11~14 Cytarabine: 2 g/m2, IV, every 12 hours, days 1~5 Mitoxantrone: 12 mg/m2/day, IV, days 1~2

Drug: Dasatinib

After the completion of each induction and consolidation chemotherapy with recovery of leukocyte and platelet counts, dasatinib will be given as an alternative manner: 100 mg by mouth once daily for 4 weeks

Other Name: Sprycel

Drug: Cyclophosphamide

300 mg/m2, IV for 2 hours, every 12 hours x 6 doses, days 1-3

Other Name: Endoxan

Drug: Vincristine

1.4 mg/m2/day (maximum 2 mg/day), IV for 30 minutes, days 4 & 11

Other Name: Vincristine sulfate

Drug: Daunorubicin

45 mg/m2/day, IV for 1 hour, days 4 & 11

Other Name: Cerubidine

Drug: Dexamethasone

40 mg/day, IV push, days 1-4 & days 11-14

Other Name: Dexamethasone disodium phosphate

Drug: Cytarabine

2 g/m2, IV for 3 hours, every 12 hours x 10 doses, days 1-5

Other Name: Cytosar U

Drug: Mitoxantrone

12 mg/m2/day, IV for 30 minutes, days 1-2

Other Name: Mitrone

Show Detailed Description

Eligibility

Ages Eligible for Study:	15 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with newly diagnosed acute lymphoblastic or biphenotypic leukemia (karyotypic or molecular evidence of Ph)
Ages of 15-65 years
Eastern Cooperative Oncology Group performance status of 0-2
Adequate renal (serum creatinine less than 2 mg/dl, unless considered due to leukemia) and hepatic (serum bilirubin less than 3 mg/dl, unless considered due to leukemia) functions
Adequate cardiac status (New York Heart Association Class less than or equal to 2)
Signed informed consent

Exclusion Criteria:

Pregnant and lactating women will not be eligible. Women of childbearing potential should have a negative pregnancy test prior to entering on the study.
Active cardiac dysfunction (New York Heart Association Class more than or equal to 3), uncontrolled angina, myocardial infarction (within 6 months), congenital long QT syndrome, any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia or ventricular fibrillation), or prolonged QTc interval on pre-entry electrocardiogram (more than 470 msec)
Patients with documented significant pleural or pericardial effusions unless they are thought to be secondary to their leukemia
Patients with severe medical conditions that in the view of the investigator prohibits participation in the study
Treatment with any other investigational antileukemic agents in the last 30 days before study entry

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01004497

Locations

Korea, Republic of
Chonbuk National University Hospital
Chonju, Chonbuk, Korea, Republic of, 561-712
Soonchunhyang University Bucheon Hospital
Bucheon, Gyeonggi-do, Korea, Republic of, 420-767
National Cancer Center
Goyang, Gyeonggi-do, Korea, Republic of, 410-769
Chonnam National University Hwasun Hospital
Hwasun, Jeonnam, Korea, Republic of, 519-809
St. Vincent's Hospital, The Catholic University of Korea
Suwon, Kyonggi-do, Korea, Republic of, 442-723
Korea University Guro Hospital
Seoul, Korea, Republic of, 152-703
Catholic BMT Center, Seoul St. Mary's Hospital, The Catholic University of Korea
Seoul, Korea, Republic of, 137-701
Yonsei University Severance Hospital
Seoul, Korea, Republic of, 120-752

Sponsors and Collaborators

The Catholic University of Korea

Investigators

Principal Investigator:

Seok Lee, M.D.

Catholic BMT Center, Seoul St. Mary's Hospital, The Catholic University of Korea

More Information

No publications provided

Responsible Party:	Seok Lee, Professor, The Catholic University of Korea
ClinicalTrials.gov Identifier:	NCT01004497 History of Changes
Other Study ID Numbers:	KC09MIMS0255
Study First Received:	October 29, 2009
Last Updated:	April 29, 2013
Health Authority:	Korea: Institutional Review Board Korea: Food and Drug Administration

Keywords provided by The Catholic University of Korea:

Acute lymphoblastic leukemia, adult, dasatinib

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Cyclophosphamide
Cytarabine

Daunorubicin
Dexamethasone
Mitoxantrone
Vincristine
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Dasatinib
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on May 23, 2013