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

December 14, 2020 updated by: Abhinav Deol, Barbara Ann Karmanos Cancer Institute

Phase I Study of Dasatinib in Recipients of Allogeneic Stem Cell Transplantation for Hematologic Malignancies.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is a phase I, dose-escalation study.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Barbara Ann Karmanos Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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.
Other: laboratory biomarker analysis
Correlative studies
Drug: Dasatinib
Patients receive dasatinib PO every day (QD) for 6 months.
Other Names:
  • BMS-354825
  • Sprycel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT) of dasatinib
Time Frame: 2 months
2 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Estimate the non-DLTs associated with administration of dasatinib in allogeneic stem cell transplantation (ASCT) recipients
Time Frame: Up to 6 months post treatment
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
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
Prior to day 1 administration of dasatinib and thereafter every 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (ACTUAL)

October 9, 2018

Study Completion (ACTUAL)

October 9, 2018

Study Registration Dates

First Submitted

May 30, 2012

First Submitted That Met QC Criteria

July 16, 2012

First Posted (ESTIMATE)

July 18, 2012

Study Record Updates

Last Update Posted (ACTUAL)

December 17, 2020

Last Update Submitted That Met QC Criteria

December 14, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011-204

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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