Dasatinib in Relapsed or Refractory Non-Hodgkin's Lymphoma

NCT00550615 | Completed Phase 1 Results DMC

• 2 other identifiers: 0244-07-FBBMS Protocol 180129
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Non-Hodgkin's Lymphoma

Keywords

Non-Hodgkins Lymphoma; Relapsed Non Hodgkins Lymphoma; Refractory Non Hodgkins Lymphoma; Dasatinib

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  after 1-28 day cycle of therapy

Secondary Outcomes (1)

• Number of Participants With Clinical Response Rates

  after 2-28 day cycles of therapy

Study Arms (2)

Dasatinib Dose Escalation

EXPERIMENTAL

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 Maximum Tolerated Dose

EXPERIMENTAL

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

Interventions

Dasatinib DRUG

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.

Also known as: Spryocel

Dasatinib Dose Escalation

Dasatinib Maximum Tolerated Dose DRUG

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

Also known as: Spryocel

Dasatinib Maximum Tolerated Dose

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• University of Nebraska: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

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

Omaha, Nebraska, 68198-7680, United States

Location

Related Publications (11)

• 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.

  PMID: 16514137 BACKGROUND

• 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.

  PMID: 9704731 BACKGROUND

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

  BACKGROUND

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

  BACKGROUND

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

  BACKGROUND

• 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.

  PMID: 16568084 BACKGROUND

• 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.

  PMID: 12533043 BACKGROUND

• 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.

  PMID: 16373702 BACKGROUND

• 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.

  PMID: 15948116 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 17242396 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Julie M Vose
• Organization: University of Nebraska Medical Center

jmvose@unmc.edu

402-559-348

Study Officials

• Julie Vose, M.D.

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2007
• First Posted: October 30, 2007
• Study Start: September 17, 2007
• Primary Completion: August 1, 2016
• Study Completion: December 1, 2017
• Last Updated: September 26, 2023
• Results First Posted: February 1, 2019

Record last verified: 2023-09

Locations

US (1)