E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
phase II: patients with follicular NHL |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025320 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
phase II: to evaluate the safety of
multiple doses of Apo2L/TRAIL administered in combination with rituximab to subjects with relapsed
follicular NHL who have progressed following stable disease or an objective response to a previous
rituximab-containing regimen, and to evaluate the efficacy of multiple doses of Apo2L/TRAIL
administered in combination with rituximab to subjects with relapsed follicular NHL, as measured by
response rate. |
|
E.2.2 | Secondary objectives of the trial |
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;
and 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 to evaluate the distribution of Fcγ receptor polymorphisms and to assess their potential
to affect clinical outcome. |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects must meet the following criteria to be eligible for study entry:
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.
Phase II Part Only: History of histologically confirmed Stage III or IV 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 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
Protocol: Apo2L/TRAILGenentech, Inc.
43/P APO3585g-A3
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)
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 [IUD], physical barrier
throughout the trial and for 1 year following their final exposure to study treatment).
Life expectancy of > 3 months
Willingness and capability to comply with the requirements of the study |
|
E.4 | Principal exclusion criteria |
Subjects who meet any of the following criteria will be excluded from study entry:
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)
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 1Pregnancy 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/μL
Platelet count < 75,000/μL
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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
objective response
(partial response or complete response [CR/CRu]) as determined by the IRF, incidence and severity of
adverse events, and changes in vital signs and clinical laboratory results. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |