Dasatinib for Modulating Immune System After Autologous Stem Cell Transplants for Multiple Myeloma, Non-Hodgkin, or Hodgkin Lymphoma

March 12, 2020 updated by: Abhinav Deol, Barbara Ann Karmanos Cancer Institute

Phase I Study of Dasatinib in Recipients of Autologous 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 blood SCT. In this research study, researchers want to find how well dasatinib can be tolerated, the best dose to take of dasatinib and 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)

8

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

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Recipients of first ASCT for the treatment of hematologic malignancies (multiple myeloma, Hodgkin's and non Hodgkin's lymphoma)
  • Patients must be between 100 to 180 days after ASCT
  • Dasatinib use prior to ASCT is allowed
  • Performance status >= 60%
  • Presence of 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 times the institutional ULN
  • Hemoglobin >= 8 g/dL
  • Absolute neutrophil counts >= 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:

  • Patients who have evidence of disease progression before day 100 after ASCT

  • Sex and reproductive status:

    • 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
  • Medical history and concurrent diseases:
  • 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 corrected QT (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 intravenous (IV) bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia
  • Other exclusion criteria:
  • Prisoners or subjects who are involuntarily incarcerated
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, 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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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. 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose limiting toxicity (DLT) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4
Time Frame: 2 months
2 months
Maximum tolerated dose (MTD)graded according to the NCI CTCAE version 4
Time Frame: 2 months
Defined as highest dose at which no more than one of dose limiting toxicity (DLT) is observed (among the first 6 patients treated and evaluable for toxicity for the purpose of cohort dose escalation decisions).
2 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of large granular lymphocytes (LGL) lymphocytosis
Time Frame: 6 months
95% confidence intervals estimated.
6 months

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 (Actual)

February 12, 2015

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

May 30, 2012

First Posted (Estimate)

June 1, 2012

Study Record Updates

Last Update Posted (Actual)

March 16, 2020

Last Update Submitted That Met QC Criteria

March 12, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011-203

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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