Sunitinib in Treating Patients With Relapsed or Refractory Diffuse or Mediastinal Large B-Cell Lymphoma

Recurrent Adult Diffuse Large Cell Lymphoma Clinical Trial

Official title:

A Phase II Study of Sunitinib (SU11248; NSC 736511; IND 74019), an Oral Multi-Targeted Tyrosine Kinase Inhibitor, in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00392496
• Other study ID #: NCI-2009-00692
• Secondary ID: NCI-2009-00692CD
• Status: Completed
• Phase: Phase 2
• First received: October 25, 2006
• Last updated: April 28, 2014
• Start date: February 2007
• Est. completion date: January 2012

Study information

• Verified date: April 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase II trial is studying how well sunitinib works in treating patients with relapsed or refractory diffuse or mediastinal large B-cell lymphoma. Sunitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.

Description:

PRIMARY OBJECTIVES:

I. Determine the response rate in patients with relapsed or refractory, diffuse or mediastinal, large B-cell lymphoma treated with sunitinib malate.

II. Determine the toxicity of this drug in these patients. III. Determine the effects of this drug on peripheral blood biomarkers, circulating endothelial cells, and their precursors in these patients.

OUTLINE: This is a non-randomized, open-label, multicenter study.

Patients receive sunitinib malate orally once daily on days 1-28. Treatment repeats every 4 weeks for a maximum of 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Criteria:

• Histologically confirmed diffuse or mediastinal large B-cell lymphoma*, meeting the following criteria: Advanced or metastatic disease, Incurable by standard therapies, Relapsed or refractory disease [Note: *Patients with diffuse large B-cell lymphoma whose disease has transformed from an earlier diagnosis of low grade lymphoma (i.e., an indolent histology) are eligible]

• Bidimensionally measurable disease** by CT scan, MRI, or physical exam, with >= 1 disease site meeting 1 of the following criteria: Lymph nodes >= 1.5 cm x 1.5 cm by spiral CT scan, Non-nodal regions >= 1 cm x 1 cm by MRI, CT scan, or physical exam [Note: **Bone lesions are not considered bidimensionally measurable disease]

• Received 1-2 prior chemotherapy regimens that included doxorubicin hydrochloride; Prior stem cell transplantation and high-dose chemotherapy is considered one regimen; One prior non-chemotherapy regimen in the form of radiation allowed; Measurable disease must be outside the previously irradiated area;

• No sole site of disease in a previously irradiated area unless progressive disease or new lesions are documented; Low-dose palliative radiotherapy may be allowed

• No known brain metastases

• Life expectancy >= 12 weeks

• ECOG performance status 0-1

• Absolute granulocyte count >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• AST and ALT =< 2.5 times upper limit of normal (ULN)

• Bilirubin normal

• Calcium =< 3 mmol/L

• Creatinine =< 1.25 times ULN OR creatinine clearance >= 60 mL/min

• LVEF normal by MUGA

• None of the following in the past 12 months: cardiac arrhythmia, cerebrovascular accident (CVA), coronary/peripheral artery bypass graft or stenting, myocardial infarction, stable or unstable angina, symptomatic congestive heart failure, transient ischemic attack, pulmonary embolism

• No uncontrolled hypertension (systolic blood pressure >= 140 mm Hg or diastolic blood pressure >= 90 mm Hg)

• No New York Heart Association (NYHA) class III or IV heart disease

• No QTc prolongation (QTc interval >= 500 msec) or other significant ECG abnormalities

• No other prior malignancies except nonmelanoma skin cancer, in situ cervical cancer, or other solid tumors curatively treated with no evidence of disease for >= 5 years

• No history of allergic reaction to compounds of similar chemical or biological composition to sunitinib malate

• No other serious illness or medical condition that would preclude study participation, including, but not limited to, the following:

active, uncontrolled infection, serious or nonhealing wound, ulcer, or bone fracture, history of significant neurologic or psychiatric disorder that would impair the ability to obtain consent or limit compliance

• Other medical condition that might be aggravated by treatment

• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days

• No bowel obstruction

• No condition that would impair the ability to swallow and retain sunitinib malate tablets, including any of the following:

Gastrointestinal tract disease resulting in inability to take oral medication or a requirement for IV alimentation, Prior surgical procedures affecting absorption, Active peptic ulcer disease

• No pre-existing hypothyroidism unless euthyroid on medication

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• At least 28 days since prior chemotherapy

• At least 28 days since prior radiotherapy and recovered; radiotherapy must have involved < 30% of functioning bone marrow

• At least 28 days since prior major surgery and recovered

• At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following: rifampin, phenytoin, rifabutin, hypericum perforatum (St. John's wort), carbamazepine, efavirenz, phenobarbital, tipranavir,

• At least 7 days since prior and concurrent CYP3A4 inhibitors, including any of the following: azole antifungals (e.g., ketoconazole, itraconazole), verapamil, clarithromycin, HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, nelfinavir), erythromycin, delavirdine, diltiazem,

• No prior therapy with other antiangiogenic agents or multitargeted tyrosine kinase inhibitors, including any of the following:

bevacizumab, sorafenib tosylate, pazopanib, thalidomide, AZD2171 vandetanib, AMG 706, vatalanib, VEGF Trap

• No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin); Concurrent dosing of =< 2 mg of warfarin daily for prophylaxis of thrombosis is allowed; Concurrent low molecular weight heparin is allowed provided INR is =< 1.5

• No other concurrent anticancer treatments, including investigational agents

• No concurrent agents with proarrhythmic potential, including any of the following:

terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, flecainide

• No concurrent combination antiretroviral therapy for HIV-positive patients

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Diffuse Large Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Recurrent Adult Diffuse Large Cell Lymphoma
• Stage IV Adult Diffuse Large Cell Lymphoma

Intervention

Drug:
• sunitinib malate
Given orally

Locations

Country	Name	City	State
Canada	National Cancer Institute of Canada Clinical Trials Group	Kingston	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Tumor Response	It is defined as per the Report of the International workshop to standardize response criteria for non-Hodgkin's lymphoma and reviewed independently	Up to 3 years	No