Dasatinib in Treating Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Barbara Ann Karmanos Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Abhinav Deol, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT01643603
First received: May 30, 2012
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Non-Hodgkin's Lymphoma
Hodgkin's Lymphoma
Myeloid Leukemia
Multiple Myeloma
Myelodysplastic Syndrome
Lymphoid Leukemia
Drug: Dasatinib
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Dasatinib in Recipients of Allogeneic Stem Cell Transplantation for Hematologic Malignancies.

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT) of dasatinib [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Estimate the non-DLTs associated with administration of dasatinib in allogeneic stem cell transplantation (ASCT) recipients [ Time Frame: Up to 6 months post treatment ] [ Designated as safety issue: Yes ]
  • Estimate the incidence of large granular lymphocytosis (LGL) and its clinical course in recipients of ASCT [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: May 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

This is a phase I, dose-escalation study followed by a phase II study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01643603

Contacts
Contact: Abhinav Deol, M.D. 313-576-8711 deola@karmanos.org

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Clinical Trials Office    800-527-6266      
Sub-Investigator: Muneer Abidi, M.D.         
Sub-Investigator: Lois Ayash, M.D.         
Sub-Investigator: Lawrence Lum, M.D.         
Sub-Investigator: Voravit Ratanatharathorn, M.D.         
Sub-Investigator: Charles Schiffer, M.D.         
Sub-Investigator: Joseph Uberti, M.D.         
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Principal Investigator: Abhinav Deol, M.D. Barbara Ann Karmanos Cancer Institute
  More Information

No publications provided

Responsible Party: Abhinav Deol, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT01643603     History of Changes
Other Study ID Numbers: 2011-204
Study First Received: May 30, 2012
Last Updated: March 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by 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:
Hodgkin Disease
Leukemia
Leukemia, Lymphoid
Leukemia, Myeloid
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Large-Cell, Immunoblastic
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Neoplasms by Site
Dasatinib
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 14, 2014