A PHASE II, RANDOMIZED, DOUBLE-BLIND,PLACEBO-CONTROLLED STUDY OF THE SAFETY,PHARMACOKINETICS, AND EFFICACY OF MULTIPLE DOSES OF APOMAB ADMINISTERED INTRAVENOUSLY IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH FOLLICULAR, CD20-POSITIVE B-CELL NON-HODGKIN’S LYMPHOMA THAT HAS PROGRESSED FOLLOWING PREVIOUS RITUXIMAB THERAPY ESTUDIO FASE II, ALEATORIZADO , DOBLE CIEGO, CONTROLADO CON PLACEBO PARA VALORAR LA SEGURIDAD, FARMACOCINÉTICA Y EFICACIA DE MULTIPLES DOSIS DE APOMAB ADMINISTRADAS POR VIA INTRAVENOSA EN COMBINACIÓN CON RITUXIMAB EN PACIENTES CON LINFOMA NON HODGKING FOLICULAR CON CELULAS B CD20 POSITIVAS QUE HAN PROGRESADO DESPUÉS DE UNA TERAPIA PREVIA CON RITUXIMAB

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2007-001666-32-ES
• Date of registration: 02/03/2010
• Prospective Registration: No
• Primary sponsor: Genentech Inc
• Public title: A PHASE II, RANDOMIZED, DOUBLE-BLIND,PLACEBO-CONTROLLED STUDY OF THE SAFETY,PHARMACOKINETICS, AND EFFICACY OF MULTIPLE DOSES OF APOMAB ADMINISTERED INTRAVENOUSLY IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH FOLLICULAR, CD20-POSITIVE B-CELL NON-HODGKIN’S LYMPHOMA THAT HAS PROGRESSED FOLLOWING PREVIOUS RITUXIMAB THERAPY ESTUDIO FASE II, ALEATORIZADO , DOBLE CIEGO, CONTROLADO CON PLACEBO PARA VALORAR LA SEGURIDAD, FARMACOCINÉTICA Y EFICACIA DE MULTIPLES DOSIS DE APOMAB ADMINISTRADAS POR VIA INTRAVENOSA EN COMBINACIÓN CON RITUXIMAB EN PACIENTES CON LINFOMA NON HODGKING FOLICULAR CON CELULAS B CD20 POSITIVAS QUE HAN PROGRESADO DESPUÉS DE UNA TERAPIA PREVIA CON RITUXIMAB
• Scientific title: A PHASE II, RANDOMIZED, DOUBLE-BLIND,PLACEBO-CONTROLLED STUDY OF THE SAFETY,PHARMACOKINETICS, AND EFFICACY OF MULTIPLE DOSES OF APOMAB ADMINISTERED INTRAVENOUSLY IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH FOLLICULAR, CD20-POSITIVE B-CELL NON-HODGKIN’S LYMPHOMA THAT HAS PROGRESSED FOLLOWING PREVIOUS RITUXIMAB THERAPY ESTUDIO FASE II, ALEATORIZADO , DOBLE CIEGO, CONTROLADO CON PLACEBO PARA VALORAR LA SEGURIDAD, FARMACOCINÉTICA Y EFICACIA DE MULTIPLES DOSIS DE APOMAB ADMINISTRADAS POR VIA INTRAVENOSA EN COMBINACIÓN CON RITUXIMAB EN PACIENTES CON LINFOMA NON HODGKING FOLICULAR CON CELULAS B CD20 POSITIVAS QUE HAN PROGRESADO DESPUÉS DE UNA TERAPIA PREVIA CON RITUXIMAB
• Date of first enrolment: 11/03/2008
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001666-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): Therapeutic use (Phase IV):

Countries of recruitment

Belgium, Netherlands, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
>Signed Informed Consent Form
> Age =18 years
>Diagnosis of follicular, CD20-positive B-cell NHL classified as Grade 1, 2, or
3a according to the WHO classification of malignant lymphomas
>Progression of disease after an objective response (CR/CRu or PR) or SD
lasting 6 months following completion of the most recent rituximab-containing regimen
>A rituximab-containing regimen is defined as rituximab as a single agent
during induction and/or maintenance, or in combination with other agents.
>Measurable disease (according to modified IWG Criteria; see Appendix B)
ECOG performance status of 0 or 1 (see Appendix D)
>Life expectancy of 3 months
>Willingness and capability to be accessible for follow-up until study
termination or death
>For patients of reproductive potential (both males and females), use of a
reliable means of contraception (e.g., contraceptive pill, intrauterine device
[IUD], barrier methods) throughout the trial and for 1 year following their last
exposure to study treatment

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:
>Grade 3b follicular lymphoma (according to the WHO classification) or
histologic transformation from follicular lymphoma to aggressive lymphoma
>Prior radiotherapy to a lesion(s) that will be used to assess response unless
that lesion(s) shows clear evidence of lymphoma progression at baseline
(i.e., =50% increase in the product of the longest perpendicular diameters of
the lesion [greatest transverse diameter perpendicular diameter] when
compared with the nadir of lesion dimensions following radiotherapy and
1.5 cm in the greatest transverse diameter)
>Radiotherapy to a peripheral lesion within 14 days prior to Cycle 1, Day 1 or
radiotherapy to a thoracic, abdominal, or pelvic field within 28 days prior to
Cycle 1, Day 1
>Prior radio-immunotherapy, including radiolabeled antibodies
>Concurrent systemic corticosteroid therapy (except low-dose corticosteroid
therapy used to treat an illness other than lymphoma)
>Other invasive malignancies within 5 years prior to Cycle 1, Day 1 (other than
basal or squamous cell carcinoma of the skin or in situ carcinoma of the
cervix treated with curative intent)
>History or evidence on physical examination of central nervous system
(CNS) disease (e.g., primary brain tumor, CNS lymphoma, seizures not
controlled with standard medical therapy, any brain metastases, or history
of stroke)
>Prior treatment with agonistic DR4 or DR5 antibodies or Apo2L/TRAIL
>General Medical Concerns
>Current or recent (within the 28 days prior to Cycle 1, Day 1) participation in
another experimental drug study
>Clinically significant cardiovascular disease (e.g., uncontrolled hypertension,
myocardial infarction within 1 year prior to Cycle 1, Day 1, unstable angina),
New York Heart Association (NYHA; see Appendix E) Grade II or greater
congestive heart failure, serious cardiac arrhythmia requiring medication
within 1 year prior to Cycle1, Day 1, or Grade II or greater peripheral vascular
disease (see Appendix F) at study entry
>Active infection requiring parenteral antibiotics on Cycle 1, Day 1
Protocol: Apomab—Genentech,
>Major surgical procedure (excluding lymph node biopsy) or significant
traumatic injury within 28 days prior to Cycle 1, Day 1, or anticipation of need
for major surgical procedure during the course of the study
>Pregnancy (positive pregnancy test) or breast feeding
>Serious, non-healing wound, ulcer, or bone fracture
Laboratory values
ANC 1500/L (may not be treated with G-CSF to maintain or exceed
this level) Platelet count 75,000/L Total bilirubin1.6 mg/dL AST or ALT 2.5 the upper limit of normal (ULN) Serum creatinine 2.0 mg/dL or measured creatinine clearance
=50 mL/min Hemoglobin 9 g/dL (may not be transfused or treated with erythropoietin to maintain or exceed this level)
>Known human immunodeficiency virus (HIV) infection, seropositivity for
hepatitis B surface antigen (HBsAg), hepatitis B IgG or IgM core antibody,
or hepatitis C virus (HCV) antibody
>History of other disease, metabolic dysfunction, physical finding,
or 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 patient at high risk from
treatment complications



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Follicular, CD20-Positive B-Cell Non-Hodgkin's Lymphoma Linfoma Non-Hodgking folicular con céluas B CD20 positivas
MedDRA version: 9.1 Level: LLT Classification code 10029593 Term: Non-Hodgkin's lymphoma NOS

Intervention(s)

Product Name: Apomab
Pharmaceutical Form: Intravenous infusion
Current Sponsor code: PRO95780
Other descriptive name: Apomab
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: up to
Concentration number: 15-
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intravenous use

Trade Name: MabThera
Product Name: Mabthera
Pharmaceutical Form: Intravenous infusion
Other descriptive name: Rituximab
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 375-

Primary Outcome(s)

Main Objective: To evaluate the safety and tolerability of Apomab when combined with rituximab for the treatment of patients with relapsed follicular, CD20-positive B-cell non-Hodgkin’s
lymphoma (NHL). To make a preliminary assessment of the efficacy of Apomab when combined with rituximab for the treatment of patients with relapsed follicular, CD20-positive B-cell NHL, as measured byobjective response rate.

Primary end point(s): Objective response (defined as a PR or CR/CRu, occurring within 8 months post-randomization), as determined by the IRF using modified IWG Criteria

Secondary Objective: To make a preliminary assessment of the efficacy of Apomab when combined with rituximab for the treatment of patients with relapsed follicular, CD20-positive B-cell NHL, as measured by progression-free survival, duration of response, and overall survival. To evaluate the serum pharmacokinetics of Apomab and rituximab when combined for the treatment of patients with relapsed follicular, CD20-positive B-cell NHL.

Secondary ID(s)

APM4083g

2007-001666-32-NL

Ethics review

Status: Approved
Approval date: 30/01/2008
Contact:

Results

• Results available: Yes
• Date Posted: 26/07/2015
• Date Completed: 31/12/2009
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-001666-32/results