PTK787 in Refractory or Relapsed Diffuse Large Cell Lymphoma

NCT ID: NCT00511043

Last Updated: 2014-12-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2010-06-30

Brief Summary

This is a phase II open label study to assess the efficacy and safety of PTK787/ZK222584 in adults with relapsed or refractory diffuse large cell lymphoma (DLCL). All subjects will receive PTK787/ZK222584. Subjects who tolerate the study target dose of 1250mg will remain on that dose until study completion at 12 months or until disease progression, unacceptable toxicity, withdrawal of consent or non-compliance with the protocol requirement.

Detailed Description

In order for tumors to grow and spread to other parts of the body, they need to have a growing blood supply. Tumor cells have been shown to produce substances that stimulate the abnormal growth of new blood vessels that allow the tumor to grow. In adults, blood vessel cells normally divide very rapidly. It is thought that PTK787/ZK222584 may interfere with the growth of new blood vessels. A drug that interferes with the growth of new blood vessels might stop tumor growth, and possibly shrink the tumor by keeping it from receiving nutrients and oxygen supplied by the blood vessels. Since normal blood vessel cells divide very rapidly, it might be possible to stop tumor growth without harming normal tissues.

The purpose of this study is to find out if an investigational drug, PTK787/ZK 222584 is safe and effective in treating relapsed or refractory diffuse large cell lymphoma.

Conditions

Lymphoma, Large-Cell, Diffuse

Keywords

PTK787; DLCL; Diffuse large cell lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All pts

PTK787

Group Type: EXPERIMENTAL

PTK787

Intervention Type: DRUG

PTK787 - 1250mg p.o. daily. Initial dose of 750mg p.o daily starting on day 1 and increased weekly to an intermediate dose of 1000 mg and then a target dose of 1250mg unless a grade ≥ 2 toxicity. Patients who tolerate the study target dose of 1250mg will remain on that dose until study completion at 12 months or until disease progression, unacceptable toxicity, withdrawal of consent or patient non-compliance with the protocol requirement.

Interventions

PTK787

PTK787 - 1250mg p.o. daily. Initial dose of 750mg p.o daily starting on day 1 and increased weekly to an intermediate dose of 1000 mg and then a target dose of 1250mg unless a grade ≥ 2 toxicity. Patients who tolerate the study target dose of 1250mg will remain on that dose until study completion at 12 months or until disease progression, unacceptable toxicity, withdrawal of consent or patient non-compliance with the protocol requirement.

Intervention Type: DRUG

Other Intervention Names

Vatalanib; ZK 222584; PTK787/ZK 222584

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed DLCL (de novo or transformed).
• Measurable/evaluable disease by radiographs, physical exam or bone marrow involvement.
• Refractory disease, induction chemotherapy failure or relapsed disease.
• Age ≥ 18 years old
• Performance Status:KPS ≥ 70
• Laboratory tests as specified by the protocol.
• Written informed consent

Exclusion Criteria

• History of known central nervous system disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis).
• History of another primary malignancy ≤ 5 years, with the exception of inactive basal or squamous cell carcinoma of the skin
• Prior chemotherapy ≤ 3 weeks prior to registration. There is no limit to the number of prior chemotherapy regimens.
• Prior allogeneic transplant if >2.5% donor cells remain by engraftment studies (prior autologous transplant is allowed)
• Prior biologic or immunotherapy ≤ 2 weeks prior to registration.
• Prior full field (total organ site) radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to registration.
• Major surgery (i.e., laparotomy) ≤ 4 weeks prior to registration. Minor surgery ≤ 2 weeks prior to registration.
• Patients who have received investigational drugs ≤ 4 weeks prior to registration and/or registration
• Prior therapy with anti-VEGF targeted agents
• Pleural effusion or ascites that causes respiratory compromise (≥ CTC grade 2 dyspnea)
• QTc > 450 (male) or > 470 (female). Patients with congenital or acquired prolonged QTc syndrome
• Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control.
• Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:

• Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen
• Unstable angina pectoris
• Symptomatic congestive heart failure
• Myocardial infarction ≤ 6 months prior to registration
• Serious uncontrolled cardiac arrhythmia
• Uncontrolled diabetes
• Severe active or uncontrolled infection
• Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
• Chronic renal disease with documented nephritic or nephrotic syndrome.
• Acute or chronic liver disease
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK787/ZK222584
• Patients with confirmed diagnosis of human immunodeficiency virus (HIV) infection are excluded at the investigator's discretion if he/she feels that 1) a potential drug interaction between PTK787/ZK 222584 and anti-HIV medications that could influence the efficacy of the anti-HIV medication, or 2) it may place the patient at risk due to the pharmacologic activity of PTK787/ZK 222584.
• Patients who are taking therapeutic warfarin sodium (Coumadin) or similar oral anticoagulants that are metabolized by the cytochrome P450 system.
• Patients unwilling to or unable to comply with the protocol
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and in the judgment of the investigator would make the patient inappropriate for entry into this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

David Rizzieri, MD

OTHER

Sponsor Role: lead

Responsible Party

David Rizzieri, MD

Associate Professor of Medicine, Division of Cellular Therapy

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David A Rizzieri, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

South Carolina Oncology Associates

Columbia, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

CPTK787AUS39

Identifier Type: -

Identifier Source: secondary_id

7416

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00008648

Identifier Type: -

Identifier Source: org_study_id