Clinical trial NCT00550615
Conditions: Non-Hodgkin's Lymphoma
Keywords: Non-Hodgkins Lymphoma Relapsed Non Hodgkins Lymphoma Refractory Non Hodgkins Lymphoma Dasatinib
Sponsor: University of Nebraska
Start date: 2007-09-17; Completion date: 2017-12-01
Enrollment: 38 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

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.

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.

Arms: arm 1: 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. arm 2: Once the maximum tolerated dose is determined, an additional patients will be enrolled into the Phase II portion of this trial.
Interventions: intervention 1: Dasatinib intervention 2: Dasatinib Maximum Tolerated Dose
Intervention descriptions: intervention 1: 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. intervention 2: An additional 29 patients using the Two-Stage Simon design will be enrolled into Phase II using the MTD determined in Phase I.

Protocol documents: