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Dasatinib for Immune Modulation After Donor Stem Cell Transplant for Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT01643603
Recruitment Status : Active, not recruiting
First Posted : July 18, 2012
Last Update Posted : January 4, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Abhinav Deol, Barbara Ann Karmanos Cancer Institute

Tracking Information
First Submitted Date  ICMJE May 30, 2012
First Posted Date  ICMJE July 18, 2012
Last Update Posted Date January 4, 2019
Study Start Date  ICMJE May 2012
Estimated Primary Completion Date January 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2012)
Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT) of dasatinib [ Time Frame: 2 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01643603 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2012)
  • Estimate the non-DLTs associated with administration of dasatinib in allogeneic stem cell transplantation (ASCT) recipients [ Time Frame: Up to 6 months post treatment ]
  • Estimate the incidence of large granular lymphocytosis (LGL) and its clinical course in recipients of ASCT [ Time Frame: Up to 6 months ]
  • Perform correlative in vitro studies to see if the large granular lymphocytes show enhanced cytotoxicity to leukemia/ lymphoma cell lines [ Time Frame: Prior to day 1 administration of dasatinib and thereafter every 4 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dasatinib for Immune Modulation After Donor Stem Cell Transplant for Hematologic Malignancies
Official Title  ICMJE Phase I/II Study of Dasatinib in Recipients of Allogeneic Stem Cell Transplantation for Hematologic Malignancies.
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 followed by a phase II study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Hodgkin's Lymphoma
  • Hodgkin's Lymphoma
  • Myeloid Leukemia
  • Multiple Myeloma
  • Myelodysplastic Syndrome
  • Lymphoid Leukemia
Intervention  ICMJE
  • Drug: Dasatinib
    Patients receive dasatinib PO every day (QD) for 6 months.
    Other Names:
    • BMS-354825
    • Sprycel
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE Experimental: Dasatinib
This is a phase 1 dose escalation study, using a standard 3+3 design. Dasatinib is administered orally once daily in the outpatient setting. Patients who are day 100-180 post transplant will be eligible. The treatment will be started as close to day 100 as possible. The range of days is provided to ensure that patients have recovered from toxicities associated with ASCT and are not deemed ineligible if they were recovering from any toxicity associated with ASCT at day 100.The starting dose of dasatinib is 20 mg daily. The increment of dose escalation is 20 mg per dose level. Thus, there will be 5 dose levels (20 mg, 40 mg, 60 mg, 80 mg and 100 mg, respectively) with 3 patients in each cohort. Patients will continue on dasatinib for 6 months.
Interventions:
  • Drug: Dasatinib
  • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: July 16, 2012)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2019
Estimated Primary Completion Date January 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01643603
Other Study ID Numbers  ICMJE 2011-204
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Abhinav Deol, Barbara Ann Karmanos Cancer Institute
Study Sponsor  ICMJE Barbara Ann Karmanos Cancer Institute
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Abhinav Deol, M.D. Barbara Ann Karmanos Cancer Institute
PRS Account Barbara Ann Karmanos Cancer Institute
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP