Follicular, CD20+, B-cell non-Hodgkin’s lymphoma. MedDRA version: 9.1 Level: LLT Classification code 10029547 Term: Non-Hodgkin's lymphoma
Conditions
Interventions
Product Name: Apo2L/TRAIL
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Apo2L/TRAIL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2
Sponsors
Genentech Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed Informed Consent Form • Age >18 years • History of histologically confirmed stage III or IV CD20+ follicular NHL Grade 1, 2, or 3a, according to the World Health Organization (WHO) classipcation system (Jaffe et al. 2001) - Histopathology will be reviewed at the study site to conprm diagnosis, and evaluation of CD20 expression will be based on the standard procedure used at each site. • Progression of disease 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. • Measurable disease (according to modified IWG criteria, see Appendix D of the protocol) • 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
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) • Prior radioimmunotherapy, including radio-labeled antibodies • 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) • 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 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 • Other invasive malignancies within 5 years prior to Day 1 (other than basal cell carcinoma of the skin or in situ carcinoma of the cervix) • 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 requiring parenteral antibiotics on Day 1 • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study and fine needle aspirations within 7 days prior to Day 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the safety of multiple doses of Apo2L/TRAIL administered in combination with rituximab to subjects with relapsed follicular NHL who have relapsed following stable disease or an objective response to a previous rituximab-containing regimen • To evaluate the efficacy of multiple administrations of Apo2L/TRAIL administered in combination with rituximab to subjects with relapsed follicular NHL, as measured by response rate;Secondary Objective: The secondary objectives of the Phase II part of this study are as follows: • To evaluate the efficacy of multiple doses of Apo2L/TRAIL administered in combination with rituximab to subjects with relapsed follicular NHL, as measured by progression-free survival, duration of response, and duration of survival • To evaluate the efficacy of multiple doses of single-agent Apo2L/TRAIL administered to subjects with relapsed follicular NHL, as measured by response rate • To evaluate the pharmacokinetics of Apo2L/TRAIL administered in combination with rituximab to subjects with relapsed follicular NHL In addition, an exploratory objective for the Phase II part of this study is as follows: • To evaluate the distribution of Fcy receptor polymorphisms and to assess their potential to affect clinical outcome.;Primary end point(s): For the Phase II part of the study, the primary endpoint is objective response through follow- up month 12 as determined using the modified IWG criteria ( see Appendix D). Objective response is defined as a complete ( CR, CRu) or partial response. Subjects without a post- baseline tumor assessment will be considered non- responders. An estimate of the objective response rate and 95% confidence intervals ( Blyth- Still- Casella) will be calculated for each treatment arm. In addition, a 95% confidence interval for the difference between treatment arms in objective response rates ( Agresti and Min 2001) will be calculated. Fisher’s exact test will be used to perform exploratory hypot | — |
Countries
Czech Republic, France, Italy
Outcome results
None listed