Dasatinib in Relapsed or Refractory Non-Hodgkin's Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00550615
First received: October 26, 2007
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

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.

Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: Dasatinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Dasatinib in Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL) (BMS Protocol 180129)

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: after 1-28 day cycle of therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical Response [ Time Frame: after 2-28 day cycles of therapy ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 47
Study Start Date: September 2007
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dose Cohort # 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

The MTD will be determined in the Phase I portion of this trial. An additional 29 patients using the Two-Stage Simon design will be enrolled into Phase II using the MTD determined in Phase I.

Other Name: Spryocel
Active Comparator: Dose Cohort # 2 Drug: Dasatinib
Dose cohort # 2 will be 150 mg per day
Active Comparator: Dose Cohort # 3 Drug: Dasatinib
Dose cohort # 3 will be 200 mg per day

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00550615

Locations
United States, Nebraska
University of Nebraska Medical Center - Internal Medicine Section of Oncology/Hematology
Omaha, Nebraska, United States, 68198-7680
Sponsors and Collaborators
University of Nebraska
Bristol-Myers Squibb
Investigators
Principal Investigator: Julie Vose, M.D. University of Nebraska
  More Information

Publications:
Hochhaus, A. et al. Dasatinib (SPRYCEL) 50mg or 70mg BID Versus 100mg or 140mg QD in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Resistant or Intolerant to Imatinib: Results of the CA180-034 Study. American Society of Hematology, 2006 Meeting Abstracts, Part 1, Volume 108, Issue 11, November 16, 2006.

Responsible Party: University of Nebraska
ClinicalTrials.gov Identifier: NCT00550615     History of Changes
Other Study ID Numbers: 244-07-FB, BMS Protocol 180129
Study First Received: October 26, 2007
Last Updated: December 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Nebraska:
Non-Hodgkins Lymphoma
Relapsed Non Hodgkins Lymphoma
Refractory Non Hodgkins Lymphoma
Dasatinib

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Dasatinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014