A Phase I/II Study of Dasatinib in Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL) (BMS Protocol 180129)
Overview
- Phase
- Phase 1
- Intervention
- Dasatinib
- Conditions
- Non-Hodgkin's Lymphoma
- Sponsor
- University of Nebraska
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility 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
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
Arms & Interventions
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.
Intervention: Dasatinib
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.
Intervention: Dasatinib Maximum Tolerated Dose
Outcomes
Primary Outcomes
Maximum Tolerated Dose
Time Frame: after 1-28 day cycle of therapy
Secondary Outcomes
- Number of Participants With Clinical Response Rates(after 2-28 day cycles of therapy)