Clinical trial NCT01643603: Dasatinib for Immune Modulation After Donor Stem Cell Transplant for Hematologic Malignancies
Official title: Phase I Study of Dasatinib in Recipients of Allogeneic Stem Cell Transplantation for Hematologic Malignancies.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-Hodgkin's Lymphoma
Hodgkin's Lymphoma
Myeloid Leukemia
Multiple Myeloma
Myelodysplastic Syndrome
Lymphoid Leukemia
Keywords: accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with del(5q)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
contiguous stage II adult Burkitt lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult lymphoblastic lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II mantle cell lymphoma
contiguous stage II marginal zone lymphoma
contiguous stage II small lymphocytic lymphoma
cutaneous B-cell non-Hodgkin lymphoma
de novo myelodysplastic syndromes
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
hepatosplenic T-cell lymphoma
intraocular lymphoma
nodal marginal zone B-cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
noncutaneous extranodal lymphoma
peripheral T-cell lymphoma
previously treated myelodysplastic syndromes
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult T-cell leukemia/lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent small lymphocytic lymphoma
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
relapsing chronic myelogenous leukemia
small intestine lymphoma
splenic marginal zone lymphoma
stage I adult Burkitt lymphoma
stage I adult diffuse large cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage I adult Hodgkin lymphoma
stage I adult immunoblastic large cell lymphoma
stage I adult lymphoblastic lymphoma
stage I adult T-cell leukemia/lymphoma
stage I chronic lymphocytic leukemia
stage I cutaneous T-cell non-Hodgkin lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage I mantle cell lymphoma
stage I marginal zone lymphoma
stage I small lymphocytic lymphoma
stage IA mycosis fungoides/Sezary syndrome
stage IB mycosis fungoides/Sezary syndrome
stage II adult Hodgkin lymphoma
stage II chronic lymphocytic leukemia
stage II cutaneous T-cell non-Hodgkin lymphoma
stage IIA mycosis fungoides/Sezary syndrome
stage IIB mycosis fungoides/Sezary syndrome
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult T-cell leukemia/lymphoma
stage III chronic lymphocytic leukemia
stage III cutaneous T-cell non-Hodgkin lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IIIA mycosis fungoides/Sezary syndrome
stage IIIB mycosis fungoides/Sezary syndrome
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult Hodgkin lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult T-cell leukemia/lymphoma
stage IV chronic lymphocytic leukemia
stage IV cutaneous T-cell non-Hodgkin lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IVA mycosis fungoides/Sezary syndrome
stage IVB mycosis fungoides/Sezary syndrome
T-cell large granular lymphocyte leukemia
testicular lymphoma
Waldenström macroglobulinemia
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2012-07-18
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This is a phase I, dose-escalation study.

Eligibility criteria: Inclusion Criteria:

* 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
* Patients must be between 100 - 180 days after allogeneic stem cell transplantation
* Dasatinib use prior to ASCT is allowed
* Performance status \>= 60%
* 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
* Total bilirubin \< 2.0 times the institutional upper limit of normal (ULN)
* Hepatic enzymes (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\] ) =\< 2.5 times the institutional ULN
* Serum creatinine \< 1.5 time the institutional ULN
* Hemoglobin \>= 8 g/dL
* Absolute neutrophil count 1,500 cells per uL
* Platelets \>= 100,000 per uL
* 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
* Patient should be able to take oral medication (dasatinib must be swallowed whole)

Exclusion Criteria:

* 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
* Patients on investigational therapy for graft-versus-host disease (GVHD)
* Patients with uncontrolled acute or chronic GVHD or refractory disease not responding to conventional therapy
* Patients who have evidence of disease progression before day 100 after ASCT
* 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
* Women who are pregnant or breastfeeding
* Women with a positive pregnancy test
* Sexually active fertile men not using effective birth control if their partners are WOCBP
* No malignancy \[other than the one treated in this study\] which required radiotherapy or systemic treatment within the past 5 years
* 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)
* 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
* Any previous history of \>= grade 3 toxicity to Dasatinib
* 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
* Prisoners or subjects who are involuntarily incarcerated
* Subjects who are compulsorily detained for treatment of either a psychiatric or physical (egg, infectious disease) illness

Primary outcomes:
measure: Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT) of dasatinib
timeFrame: 2 months
Secondary outcomes:
measure: Estimate the non-DLTs associated with administration of dasatinib in allogeneic stem cell transplantation (ASCT) recipients
timeFrame: Up to 6 months post treatment
measure: Estimate the incidence of large granular lymphocytosis (LGL) and its clinical course in recipients of ASCT
timeFrame: Up to 6 months
measure: Perform correlative in vitro studies to see if the large granular lymphocytes show enhanced cytotoxicity to leukemia/ lymphoma cell lines
timeFrame: Prior to day 1 administration of dasatinib and thereafter every 4 weeks
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Abhinav Deol, M.D.
role: PRINCIPAL_INVESTIGATOR
References: