AzTrials
AzTrials

Non-Hodgkin's LymphomaPhase 1/2NCT00550615

Dasatinib in Relapsed or Refractory Non-Hodgkin's Lymphoma

A Phase 1/2 study testing Dasatinib and Dasatinib Maximum Tolerated Dose in people with Non-Hodgkin's Lymphoma, run by University of Nebraska at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Non-Hodgkin's Lymphoma
What is being tested?
Dasatinib and Dasatinib Maximum Tolerated Dose
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteUnited States
Study dates
17 Sep 2007to 1 Dec 2017
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 16Show fewer
  • 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

Who cannot join

  • 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)
Show all 25Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Nebraska Medical Center, Internal Medicine Section of Oncology/Hematology

    Omaha, Nebraska, 68198-7680

Other trials in United States

About this study

Official title: 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.
Read the 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.

Being tested
Dasatinib, Dasatinib Maximum Tolerated Dose
Keywords
Non-Hodgkins Lymphoma, Relapsed Non Hodgkins Lymphoma, Refractory Non Hodgkins Lymphoma, Dasatinib
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DasatinibDrug

    Also called Spryocel

    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.

  • Dasatinib Maximum Tolerated DoseDrug

    Also called Spryocel

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

Study groups in NCT00550615
Study groupRoleWhat they receive
Dasatinib Dose EscalationExperimentalPhase 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.
Receives: Drug: Dasatinib
Dasatinib Maximum Tolerated DoseExperimentalOnce the maximum tolerated dose is determined, an additional patients will be enrolled into the Phase II portion of this trial.
Receives: Drug: Dasatinib Maximum Tolerated Dose

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose

    Measured: after 1-28 day cycle of therapy

Secondary outcomes (1)

  1. Number of Participants With Clinical Response Rates

    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.

    Measured: after 2-28 day cycles of therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2007 (estimated)
  2. Study start17 Sep 2007
  3. Primary completion1 Aug 2016
  4. Study completion1 Dec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00550615
Sponsor's protocol ID
0244-07-FB
Other IDs
BMS Protocol 180129
Status last verified
Sep 2023
First submitted
26 Oct 2007
Last updated
26 Sep 2023
Data monitoring committee
Yes

Publications

  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics, 2006. CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30. doi: 10.3322/canjclin.56.2.106.

    PubMed 16514137

  • Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol. 1998 Aug;16(8):2780-95. doi: 10.1200/JCO.1998.16.8.2780.

    PubMed 9704731

  • SPRYCEL (dasatinib) Tablets Prescribing Information. Bristol-Myers Squibb Company, Princeton, NJ. June 2006

  • SPRYCEL® (dasatinib) BMS-354825 Bristol-Myers Squibb Investigator Brochure, Version #5, 2006.

  • SPRYCEL® (dasatinib) BMS-354825 Bristol-Myers Squibb Investigator Brochure, Version #6 in print, 2006.

  • Sprangers M, Feldhahn N, Herzog S, Hansmann ML, Reppel M, Hescheler J, Jumaa H, Siebert R, Muschen M. The SRC family kinase LYN redirects B cell receptor signaling in human SLP65-deficient B cell lymphoma cells. Oncogene. 2006 Aug 17;25(36):5056-62. doi: 10.1038/sj.onc.1209510. Epub 2006 Mar 27.

    PubMed 16568084

  • Zhu DM, Tibbles HE, Vassilev AO, Uckun FM. SYK and LYN mediate B-cell receptor-independent calcium-induced apoptosis in DT-40 lymphoma B-cells. Leuk Lymphoma. 2002 Nov;43(11):2165-70. doi: 10.1080/1042819021000032935.

    PubMed 12533043

  • Mahadevan D, Spier C, Della Croce K, Miller S, George B, Riley C, Warner S, Grogan TM, Miller TP. Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures. Mol Cancer Ther. 2005 Dec;4(12):1867-79. doi: 10.1158/1535-7163.MCT-05-0146.

    PubMed 16373702

  • Thompson MA, Stumph J, Henrickson SE, Rosenwald A, Wang Q, Olson S, Brandt SJ, Roberts J, Zhang X, Shyr Y, Kinney MC. Differential gene expression in anaplastic lymphoma kinase-positive and anaplastic lymphoma kinase-negative anaplastic large cell lymphomas. Hum Pathol. 2005 May;36(5):494-504. doi: 10.1016/j.humpath.2005.03.004.

    PubMed 15948116

  • 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.

  • Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.

    PubMed 17242396

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dasatinib and Dasatinib Maximum Tolerated Dose in people with Non-Hodgkin's Lymphoma, run by University of Nebraska at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (time frame: after 1-28 day cycle of therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00550615, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in