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
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