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

NCT01004497 | Completed Phase 2 DMC

• 1 other identifier: KC09MIMS0255
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Acute lymphoblastic leukemia, adult, dasatinib

Outcome Measures

Primary Outcomes (1)

• To determine the clinical efficacy of dasatinib plus conventional chemotherapy for newly diagnosed Ph-positive ALL in terms of major molecular response rate

  by the second 4-week dasatinib therapy

Secondary Outcomes (1)

• To evaluate the long-term clinical outcomes (including transplant outcomes) in terms of treatment toxicity, relapse, disease-free survival, and overall survival

  at 2 years after transplantation (for all transplants); at 2 years after starting dasatinib maintenance (for all non-transplants)

Study Arms (1)

Modified Hyper-CVAD + Dasatinib

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Cytarabine; Drug: Mitoxantrone

Interventions

Dasatinib DRUG

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

Also known as: Sprycel

Modified Hyper-CVAD + Dasatinib

Cyclophosphamide DRUG

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

Also known as: Endoxan

Modified Hyper-CVAD + Dasatinib

Vincristine DRUG

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

Also known as: Vincristine sulfate

Modified Hyper-CVAD + Dasatinib

Daunorubicin DRUG

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

Also known as: Cerubidine

Modified Hyper-CVAD + Dasatinib

Dexamethasone DRUG

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

Also known as: Dexamethasone disodium phosphate

Modified Hyper-CVAD + Dasatinib

Cytarabine DRUG

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

Also known as: Cytosar U

Modified Hyper-CVAD + Dasatinib

Mitoxantrone DRUG

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

Also known as: Mitrone

Modified Hyper-CVAD + Dasatinib

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Catholic University of Korea: lead

Study Sites (8)

Soonchunhyang University Bucheon Hospital

Bucheon-si, Gyeonggi-do, 420-767, South Korea

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 410-769, South Korea

Location

Chonbuk National University Hospital

Jeonju, Jeollabuk-do, 561-712, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 519-809, South Korea

Location

St. Vincent's Hospital, The Catholic University of Korea

Suwon, Kyonggi-do, 442-723, South Korea

Location

Yonsei University Severance Hospital

Seoul, 120-752, South Korea

Location

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

Seoul, 137-701, South Korea

Location

Korea University Guro Hospital

Seoul, 152-703, South Korea

Location

Related Publications (1)

• Yoon JH, Yhim HY, Kwak JY, Ahn JS, Yang DH, Lee JJ, Kim SJ, Kim JS, Park SJ, Choi CW, Eom HS, Park SK, Choi SY, Kim SH, Kim DW, Lee S. Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Ann Oncol. 2016 Jun;27(6):1081-1088. doi: 10.1093/annonc/mdw123. Epub 2016 Mar 6.

  PMID: 26951627 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Dasatinib; Cyclophosphamide; Vincristine; Daunorubicin; Dexamethasone; dexamethasone 21-phosphate; Cytarabine; Mitoxantrone

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Cytidine; Pyrimidine Nucleosides; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthraquinones; Anthrones; Anthracenes; Quinones

Study Officials

• Seok Lee, M.D.

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

  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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 29, 2009
• First Posted: October 30, 2009
• Study Start: March 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2015
• Last Updated: May 29, 2015

Record last verified: 2015-05

Locations

KR (8)