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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01643603
Recruitment Status : Terminated (Study terminated due to slow accrual.)
First Posted : July 18, 2012
Last Update Posted : December 17, 2020
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Abhinav Deol, Barbara Ann Karmanos Cancer Institute

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.

Condition or disease Intervention/treatment Phase
Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Myeloid Leukemia Multiple Myeloma Myelodysplastic Syndrome Lymphoid Leukemia Drug: Dasatinib Other: laboratory biomarker analysis Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Dasatinib in Recipients of Allogeneic Stem Cell Transplantation for Hematologic Malignancies.
Study Start Date : May 2012
Actual Primary Completion Date : October 9, 2018
Actual Study Completion Date : October 9, 2018

Arm Intervention/treatment
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.
Drug: Dasatinib
Patients receive dasatinib PO every day (QD) for 6 months.
Other Names:
  • BMS-354825
  • Sprycel

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT) of dasatinib [ Time Frame: 2 months ]

Secondary Outcome Measures :
  1. Estimate the non-DLTs associated with administration of dasatinib in allogeneic stem cell transplantation (ASCT) recipients [ Time Frame: Up to 6 months post treatment ]
  2. Estimate the incidence of large granular lymphocytosis (LGL) and its clinical course in recipients of ASCT [ Time Frame: Up to 6 months ]
  3. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01643603

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United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
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Principal Investigator: Abhinav Deol, M.D. Barbara Ann Karmanos Cancer Institute
  Study Documents (Full-Text)

Documents provided by Abhinav Deol, Barbara Ann Karmanos Cancer Institute:
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Responsible Party: Abhinav Deol, Principal Investigator, Barbara Ann Karmanos Cancer Institute Identifier: NCT01643603    
Other Study ID Numbers: 2011-204
First Posted: July 18, 2012    Key Record Dates
Last Update Posted: December 17, 2020
Last Verified: December 2020
Keywords provided by Abhinav Deol, Barbara Ann Karmanos Cancer Institute:
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
Additional relevant MeSH terms:
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Leukemia, Myeloid
Multiple Myeloma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Hematologic Neoplasms
Leukemia, Lymphoid
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Neoplasms by Site