Dasatinib in Treating Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Basic Trial Information
|Phase II, Phase I||Biomarker/Laboratory analysis, Treatment||18 and over||CA-180-384|
NCI-2012-00773, 2011-204, NCT01643603
This study uses a drug called dasatinib to produce an anti-cancer effect called large granular lymphocyte cellular expansion. Large granular lymphocytes are blood cells known as natural killer cells that remove cancer cells. Researchers think that dasatinib may cause large granular lymphocyte expansion to happen in patients who have received a blood stem cell transplant (SCT) between 3 to 15 months after the SCT. In this research study, researchers want to find how well dasatinib can be tolerated, the best dose to take of dasatinib and how to estimate how often large granular lymphocytic cellular expansion happens at the best dose of dasatinib.
Further Study Information
I. To establish the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of dasatinib in the recipient of allogeneic stem cell transplantation (ASCT) for hematologic malignancies.
I. To estimate the non-DLTs associated with administration of dasatinib in ASCT recipients.
II. To estimate the incidence of large granular lymphocytosis (LGL) and its clinical course in recipients of ASCT.
III. To perform correlative in vitro studies to see if the large granular lymphocytes show enhanced cytotoxicity to leukemia/ lymphoma cell lines.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive dasatinib orally (PO) once daily (QD) for 6 months.
Serum creatinine < 1.5 time the institutional ULN
Hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] ) =< 2.5 times the institutional ULN
Total bilirubin < 2.0 times the institutional upper limit of normal (ULN)
Patient should be able to take oral medication (dasatinib must be swallowed whole)
Platelets >= 100,000 per uL
Absolute neutrophil count 1,500 cells per uL
Hemoglobin >= 8 g/dL
Patient should be able to provide signed written informed consent:
Before any study procedures are performed, subjects will have the details of the study described to them, and they will be given a written informed consent document to read; then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel
Written consent will include a Health Insurance Portability and Accountability Act (HIPAA) form according to institutional guidelines
Performance status >= 60%
Dasatinib use prior to ASCT is allowed
Patients must be between 100 - 180 days after allogeneic stem cell transplantation
Presence of large granular lymphocyte (LGL) clone prior to enrollment will not be an exclusion criterion if the LGL clone is < 25% of T cell population
Recipients of first ASCT from related or unrelated donor for the treatment of hematologic malignancies (acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, myelodysplastic syndrome, Hodgkin and non-Hodgkin lymphoma) who are 1-antigen or 1-allele mismatched or fully matched at human leukocyte antigen (HLA)-A, -B, -C and –DR as defined by high resolution typing
Sexually active fertile men not using effective birth control if their partners are WOCBP
Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after the last dose of study drug
Patients with uncontrolled acute or chronic GVHD or refractory disease not responding to conventional therapy
Women who are pregnant or breastfeeding
Concurrent medical condition which may increase the risk of toxicity, including:
Pleural or pericardial effusion of any grade at the time of screening for study
Cardiac Symptoms; any of the following should be considered for exclusion:
- Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months)
- Diagnosed congenital long QT syndrome
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
- Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
Any previous history of >= grade 3 toxicity to Dasatinib
History of significant bleeding disorder unrelated to cancer, including:
Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)
Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
Ongoing or recent (=< 3 months) significant gastrointestinal bleeding
Patients who have evidence of disease progression before day 100 after ASCT
Patients on investigational therapy for graft-versus-host disease (GVHD)
Recipient of mismatched (allele or antigen level) graft in more than one loci of HLAA, -B, -C or –DR loci will not be eligible, i.e. recipients of 2-antigen or 2-allelele mismatched graft
No malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 5 years
Women with a positive pregnancy test
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (egg, infectious disease) illness
Prisoners or subjects who are involuntarily incarcerated
Prohibited treatments and or therapies:
Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib)
- Quinidine, procainamide, disopyramide
- Amiodarone, sotalol, ibutilide, dofetilide
- Erythromycin, clarithromycin
- Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
- Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine,
- Domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before starting dasatinib)
Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
Wayne State University/Karmanos Cancer Institute
- National Cancer Institute
Barbara Ann Karmanos Cancer Institute
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01643603
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.