DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Dasatinib Combined With Chemotherapy in Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

Information source: Institute of Hematology & Blood Diseases Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute,Leukemia, Lymphoid

Intervention: Dasatinib (Drug); prednisone (Drug); cyclophosphamide (Drug); daunorubicin (Drug); vincristine (Drug); cytarabine (Drug); mercaptopurine (Drug); methotrexate (Drug); dexamethasone (Drug); mitoxantrone (Drug); etoposide (Drug); allogeneic hematopoietic stem cell transplantation (Procedure); autologous hematopoietic stem cell transplantation (Procedure)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Institute of Hematology & Blood Diseases Hospital

Official(s) and/or principal investigator(s):
Jianxiang Wang, Dr., Principal Investigator, Affiliation: Institute of Hematology & Blood Diseases Hospital

Overall contact:
Lijun Liu, Phone: 86-22-23909237, Email: bloodgcp@126.com

Summary

In this single-center, open-label, no control,prospective clinical trial, a total of 30 Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients will be enrolled. Dasatinib 100 mg per day will be given orally along with combination chemotherapy starting day 8 of induction chemotherapy. Dasatinib will be given continuously (if it's tolerable) for 2 years since achievement of complete remission (CR) as part of consolidation chemotherapy and maintenance therapy. Patients can receive allogeneic hematopoietic stem cell transplantation (HSCT) or autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation chemotherapy. The purpose of current study is to determine the clinical efficacy and tolerability of combination therapy of Dasatinib with multi-agent chemotherapy in newly-diagnosed Ph+ ALL.

Clinical Details

Official title: Dasatinib Plus Multi-agent Chemotherapy for New Diagnosed Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Overall survival (OS)

Secondary outcome:

Disease-free survival (DFS)

The complete remission (CR) rate

The molecular CR rate

The plasma level of dasatinib in the regimen

The Cerebrospinal fluid level of dasatinib in the regimen

Number of adverse event of combined treatment

Grade of adverse event of combined treatment

Detailed description: In this single-center, open-label, Phase II study, nonrandomized,no control,prospective clinical trial,a total of 30 Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients will be enrolled. Patients will be diagnosed according to morphologic,immunologic, cytogenetic and molecular(MICM) criteria, including bone marrow morphology, immunophenotype, cytogenetic and molecular genetic (BCR/ABL gene, qualitative and quantitative analysis) examination. Dasatinib 100 mg per day will be given orally along with combination chemotherapy starting day 8 of induction chemotherapy. Dasatinib will be given continuously (if it's tolerable) for 2 years since achievement of complete remission (CR) as part of consolidation chemotherapy and maintenance therapy. Patients can receive allogeneic hematopoietic stem cell transplantation (HSCT),or patients who keep BCR/ABL negative can receive autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation chemotherapy. Total duration of follow-up will be 2 year after last enrollment. Pre-treatment evaluation will include complete blood count (CBC) with reticulocyte count, chemistry, electrolytes, coagulation, hepatitis profile, chest X-ray. Evaluation during treatment will include: CBC every two days during myelosuppression, chemistry, electrolytes, coagulation before each cycles of chemotherapy. Quantitative PCR (RQ-PCR) for Bcr-Abl will be done from bone marrow mononuclear cells at diagnosis, at CR, and before each cycles of consolidation chemotherapy,then every 3 months during maintenance therapy. For patients who undergo allogeneic HSCT, quantitative PCR for Bcr-Abl will be done from bone marrow mononuclear cells at the initiation of conditioning, and then every 3 months. PCR will be done in IS standardized lab. Side effects of combination therapy will be monitored and described according to Common Toxicity Criteria, version 4. 0 (National Cancer Institute, USA). The purpose of current study is to determine the clinical efficacy and tolerability of combination therapy of Dasatinib with multi-agent chemotherapy in newly-diagnosed Ph+ ALL.

Eligibility

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Patients aged 18 to 60 years with De novo Philadelphia chromosome positive (Philadelphia chromosome positive or BCR/ABL transcript positive) acute lymphoblastic leukemia. 2. Eastern Cooperative Oncology Group (ECOG) Performance status 2. 3. Adequate end organ function as defined by: Total bilirubin ≤ 1. 5 x upper limit of normal(ULN); serum glutamic-oxaloacetic transaminase(SGOT) and serum glutamic pyruvic transaminase(SGPT) ≤ 2. 5 x ULN; Creatinine ≤ 1. 5 x ULN; Serum amylase and lipase ≤ 1. 5 x ULN; Alkaline phosphatase ≤ 2. 5 x ULN unless considered tumor related; Patients must have adequate cardiac function (ejection fraction ≥ 45 % on Multiple Gated Acquisition (MUGA) scan). 4. Patients must have the following laboratory values (≥ lower limit of normal (LLN) or corrected to within normal limits with supplements prior to the first dose of study medication.): Potassium ≥ LLN; Magnesium ≥ LLN; Phosphorus ≥ LLN 5. Patients should sign informed consent form. Exclusion Criteria: 1. Impaired cardiac function: Long QT syndrome or a known family history of long QT syndrome; clinically significant resting brachycardia (<50 beats per minute); ejection fraction < 45 % on MUGA scan. QTc interval > 450 msec on baseline ECG (using the QTcF formula). If QTcF interval>450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc. Myocardial infarction within 12 months prior to starting study; other clinically significant heart disease (e. g. unstable angina, congestive heart failure or uncontrolled hypertension, uncontrolled arrhythmias). Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. 2. Other concurrent severe and/or uncontrolled medical conditions: Patients with another primary malignant disease, except those that do not currently require treatment; acute or chronic liver, pancreatic or severe renal disease; another severe and/or life-threatening medical disease. 3. Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) male or female of childbearing potential unwilling to use contraceptive precautions throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential). 4. Who is known human deficiency virus (HIV) positive. 5. Use of any other investigational agent in the last 30 days.

Locations and Contacts

Lijun Liu, Phone: 86-22-23909237, Email: bloodgcp@126.com

Institute of Hematology & Blood Diseases Hospital, Tianjin, Tianjin 300020, China; Not yet recruiting
Liujun Liu, Phone: 86-22-23909237, Email: bloodgcp@126.com
Jianxiang Wang, Dr., Principal Investigator
Ying Wang, Dr., Sub-Investigator
Additional Information

Starting date: August 2015
Last updated: August 13, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017