Dasatinib in Relapsed or Refractory Non-Hodgkin's Lymphoma

September 16, 2023 updated by: University of Nebraska

A Phase I/II Study of Dasatinib in Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL) (BMS Protocol 180129)

Primary Objective:

  • To determine the maximum tolerated dose (MTD) of Dasatinib in relapsed or refractory non-hodgkin's lymphoma (NHL) patients and to determine the safety of Dasatinib in NHL.

Secondary Objectives:

  • To assess the complete and overall response rates for all Phase I and Phase II patients and to determine overall survival and event free survival for all Phase I and Phase II patients.
  • To assay the levels of kinase activity in NHL specimens and correlate this activity to patient outcomes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Primary:

  • To determine the Maximum Tolerated Dose (MTD) of Dasatinib in relapsed or refractory Non-Hodgkin's lymphoma (NHL) patients and to determine the safety of Dasatinib in NHL

Secondary Objective:

  • To assess the complete and overall response rates for all Phase I and Phase II patients and to assay the levels of kinase activity in NHL specimens and correlate this activity to patient outcomes.
  • To determine overall survival and event free survival for all Phase I and Phase II patients.

Treatment Plan

This study has two phases of treatment, Phase I and Phase II. The Phase I portion of the trial will consist of a dose escalation plan with 3-6 patients being enrolled into each dose cohort. The doses of Dasatinib used in Phase I are 100 mg, 150 mg, and 200 mg. The dose that is found to be tolerated the best and also has the best treatment results will be used for Phase II. An additional 29 patients will be enrolled into Phase II.

All patients will receive Dasatinib in this study. Dasatinib will be administered orally (by mouth) once daily for 28 day cycles. A cycle will be considered 28 days. Dosing will be continuous with no interruptions, unless instructed to interrupt treatment by the treating physician.

The patient will be restaged after every 2 cycles of therapy, every even cycle. Therapy may continue as long as there are no clinical signs of NHL progressing and the patient is tolerating the treatment with no side effects related to the therapy. If the patient is removed from study for any reason, he/she will be followed for survival until death.

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 2
  • 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
    • Nebraska
      • Omaha, Nebraska, United States, 68198-7680
        • University of Nebraska Medical Center, Internal Medicine Section of Oncology/Hematology

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

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed diagnosis of non-hodgkin's lymphoma that is recurrent or refractory after at least one prior therapy and for which no other potentially curative therapy is available.
  • Subject, age > or = 19 years
  • Performance status (ECOG) 0-2
  • Patients must have relapsed or refractory disease after at least one prior systemic therapy, with at least a 3 week interval from the completion of the most recent chemotherapy or radiotherapy regimen. Recover to ≤ grade 1 from all toxicities related to the prior treatments is required.
  • Patients must be ineligible or relapsed after an autologous or allogeneic stem cell transplant if clinically appropriate.

  • Adequate Laboratory Parameters:

    • ANC ≥ 1000/μL
    • Platelet count ≥ 50,000/μL
    • Total bilirubin < 2.0 times the institutional upper limit of normal (ULN)
    • Hepatic enzymes (AST, ALT ) ≤ 2.5 times the institutional ULN
    • Serum creatinine < 2.0 times the institutional ULN
    • PTT within institutional normal limits
  • Ability to take oral medication (dasatinib must be swallowed whole)
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (sensitivity < or = 25IU HCG/L) within 72 hours prior to the start of study drug administration
  • Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 6 months after study drug is stopped
  • Signed written informed consent including HIPAA according to institutional guidelines

Exclusion Criteria:

  • No malignancy [other than the one treated in this study] which required systemic treatment within the past 3 years.

  • Concurrent medical condition which may increase the risk of toxicity, including:

    • Clinically significant pleural or pericardial effusion
    • Clinically-significant coagulation or platelet function disorder (e.g. known von Willebrand's disease)

  • Cardiac Symptoms, consider the following:

    • Uncontrolled angina, congestive heart failure or 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)
    • Subjects with hypokalemia or hypomagnesemia if it cannot be corrected

  • 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 (< or = 3 months) significant gastrointestinal bleeding

  • Concomitant Medications, consider the following prohibitions:

    • 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.
    • The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is not recommended. The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy.
    • Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy
    • Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
    • Patient may not be receiving any prohibited CYP3A4 inhibitors

  • Women:

    • Are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks 6 months after cessation of study drug
    • Have a positive pregnancy test at baseline
    • Are pregnant or breastfeeding
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) 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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dasatinib Dose Escalation
Phase 1 employed a standard 3+3 dose-escalation design to assess safety, MTD and dose-limiting toxicity (DLT). Maximum Tolerated Dose (MTD) was defined as the next lowest dose level below where ≥ 2/3 or ≥ 3/6 patients experience dose limiting toxicities in cycle 1.
Drug: Dasatinib

Dasatinib will be orally administered once daily for 28 day cycles.

There will be three dose cohorts for the Dasatinib in the Phase I portion of this trial. A minimum of three patients will be enrolled into each of the following dose cohorts:

Dose cohort # 1 will be 100 mg per day Dose cohort # 2 will be 150 mg per day Dose cohort # 3 will be 200 mg per day

The MTD will be determined in the Phase I portion of this trial.

Other Names:
  • Spryocel
Experimental: Dasatinib Maximum Tolerated Dose
Once the maximum tolerated dose is determined, an additional patients will be enrolled into the Phase II portion of this trial.
Drug: Dasatinib Maximum Tolerated Dose
An additional 29 patients using the Two-Stage Simon design will be enrolled into Phase II using the MTD determined in Phase I.
Other Names:
  • Spryocel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum Tolerated Dose
Time Frame: after 1-28 day cycle of therapy
after 1-28 day cycle of therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Clinical Response Rates
Time Frame: after 2-28 day cycles of therapy

The Objective response rate (CR+PR) and the Clinical Benefit Rate (CR+PR+SD) were calculated according to revised response criteria for malignant lymphoma (Cheson) CR - Complete response is defined as: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy.

PR - Partial response is defined as: ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses.

SD - Stable Disease is define as: Failing to attain the criteria needed for a PR, but not fulfilling those for progressive disease.
after 2-28 day cycles of therapy

Collaborators and Investigators

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

Sponsor

University of Nebraska

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Julie Vose, M.D., University of Nebraska

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

September 17, 2007

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

December 1, 2017

Study Registration Dates

First Submitted

October 26, 2007

First Submitted That Met QC Criteria

October 29, 2007

First Posted (Estimated)

October 30, 2007

Study Record Updates

Last Update Posted (Actual)

September 26, 2023

Last Update Submitted That Met QC Criteria

September 16, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0244-07-FB
  • BMS Protocol 180129 (Other Grant/Funding Number: Bristol-Myers Squibb Company)

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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