A PHASE Ib/II, OPEN-LABEL, MULTICENTER STUDY OF THE SAFETY, PHARMACOKINETICS, AND EFFICACY OF Apo2L/TRAIL ADMINISTERED INTRAVENOUSLY IN COMBINATION WITH RITUXIMAB TO SUBJECTS WITH FOLLICULAR AND OTHER LOW-GRADE, CD20', B-CELL NON-HODGKIN’S LYMPHOMAS THAT HAVE PROGRESSED FOLLOWING PREVIOUS RITUXIMAB THERAPY

• Conditions: Follicular, CD20', B-cell non-Hodgkin’s lymphoma.; MedDRA version: 9.1Level: LLTClassification code 10029547Term: Non-Hodgkin's lymphoma

• Registration Number: EUCTR2006-005552-33-CZ
• Lead Sponsor: Genentech Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-06-20
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

• Signed Informed Consent Form

• Age >18 years

• Phase Ib Part Only: History of histologically confirmed Stage III or IV CD20+ low-grade small lymphocytic lymphoma or marginal zone B-cell lymphoma, or follicular NHL (any grade), according to the World Health Organization (WHO) classification system (Jaffe et al. 2001)

- Histopathology will be reviewed at the study site to confirm diagnosis, and evaluation of CD20 expression will be based on the standard procedure used at each site. In order to confirm eligibility, a repeat biopsy during the screening period should be performed if there is a clinical suspicion of histologic transformation.

• Phase II Part Only: History of histologically confirmed CD20+ follicular NHL Grade 1, 2, or 3a, according to the World Health Organization (WHO) classification system (Jaffe et al. 2001)

- Histopathology will be reviewed at the study site to confirm diagnosis,
and evaluation of CD20 expression will be based on the standard procedure used at each site.

• Progression of disease (as assessed using IWG criteria) following the most recent treatment with rituximab-containing therapy that resulted in stable disease or a partial or complete response lasting >6 months

- The rituximab-containing therapy does not have to be the last anti-tumor therapy received. There may have been more than one previous rituximab-containing therapy, but the most recent rituximab-containing therapy received has to have resulted in stable disease or a response of >6 months duration after completion of the therapy.

• Measurable disease (according to modiped IWG criteria, see Appendix D)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix F)

• For subjects of reproductive potential (males and females), use of a reliable means of contraception (e.g., contraceptive pill, intrauterine device [IUDJ, physical barrier throughout the trial and for 1 year following their pnal exposure to study treatment).

• Life expectancy of > 3 months

• Willingness and capability to comply with the requirements of the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Prior radiotherapy to a measurable, metastatic lesion(s) to be used to measure response unless that lesion shows unequivocal progression at baseline

• Radiation therapy to a peripheral lesion within 14 days prior to Day 1; Radiation therapy to a thoracic, abdominal, or pelvic field within 28 days prior to Day 1

• Chemotherapy, hormonal therapy, radiotherapy, or immunotherapy within 4 weeks prior to Day 1 (6 weeks for nitrosoureas or mitomycin)

• Subjects who have received radioimmunotherapy for relapsed or refractory, follicular NHL are eligible for the study if they received this therapy at least 1 year prior to Cycle 1, Day 1, have adequate bone marrow function (as defined by minimal hemoglobin, ANC, and platelet count requirements), and have no evidence of myelodysplastic syndrome on bone marrow aspirate/biopsy (as evidenced by cytogenetic or fluorescence in situ hybridization criteria)

• Prior treatment with Apo2L/TRAIL or an agonist antibody to DR4 or DR5

• Concurrent systemic corticosteroid therapy (except low-dose corticosteroid therapy used to treat an illness other than lymphoma or single administrations of hydrocortisone up to 100 mg per dose, prior to rituximab infusions for prophylaxis against severe infusion reaction)

• Pregnancy or lactation

• Serious nonhealing wound, ulcer, or bone fracture

• Current or recent (within the 28 days prior to Day 1) participation in another experimental drug study

• Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix B), serious ventricular cardiac arrhythmia requiring medication within 1 year prior to Day 1, Grade II or greater peripheral vascular disease on Day 1 (see Appendix G)

• Clinical laboratory values
- ANC <1500/pL
- Platelet count <75,000/pL
- Hemoglobin <9 g/dL (may not be transfused or treated with erythropoietin to maintain or exceed this level)
- Total bilirubin >1.6 mg/dL
- AST or ALT >2.5 times the upper limit of normal
- Serum creatinine >2.0 mg/dL or measured creatinine clearance < 50 mL/min.

• Known positive test result for HIV, hepatitis B surface antigen (sAg), hepatitis B IgG or IgM core antibody, or hepatitis C antibody

• Known sensitivity to murine or human antibodies

• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications

• Evidence of clinically detectable ascites on Day 1 (small pleural and peritoneal effusions detected incidentally on screening CT scans are not exclusionary)

Other invasive malignancies within 3 years prior to first study drug administration except for adequately treated (with curative intent) basal or squamous cell skin cancer, in situ carcinoma of the cervix, in situ breast cancer, in situ prostate cancer, limited-stage bladder cancer, or other cancers from which the subject has been disease free for at least 3 years.

• History or evidence upon physical examination of CNS disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke) within 1 year prior to study entry

• Active infection

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified