A randomized Phase III clinical trial to compare the efficacy and safety of the biosimilar rituximab GP2013 in combination with a standard chemotherapy (CVP) or rituximab MabThera in combination with a standard chemotherapy (CVP), including GP2013/MabThera maintenance therapy in patient with previously untreated advanced stage follicular lymphoma.

• Conditions: Advanced stage follicular lymphoma.; MedDRA version: 17.1Level: PTClassification code 10016910Term: Follicle centre lymphoma, follicular grade I, II, III stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 17.1Level: PTClassification code 10016909Term: Follicle centre lymphoma, follicular grade I, II, III stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-019522-13-DE
• Lead Sponsor: HEXAL AG (a Sandoz company)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-08-31
• Last Update Posted: 1 February 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 618

Inclusion Criteria

following criteria:
1. Patient with previously untreated advanced stage, CD20-positive FL:
a. Ann Arbor classification stage III/IV;
b. WHO histologic grade 1, 2 or 3a, as confirmed by central
pathological testing; and
c. Require therapy for FL as per local guidelines or in the opinion of
the treating physician.
2. Patient age = 18 years.
3. Patient with at least one measurable lesion (accurately measurable in
at least 2 perpendicular dimensions);
a. at least 1 measurable nodal lesion > 20 mm in the long axis; OR
b. at least 1 measurable extranodal lesion with both long and short
axes = 10 mm.
4. Patient with ECOG performance status 0, 1 or 2.
5. Patient with adequate cardiac function defined as cardiac ejection
fraction = 45% as measured by ECHO or MUGA, without clinically
significant abnormalities.
6. Patient with the following laboratory values obtained during
Screening (up to 28 days before randomization):
a. hemoglobin = 10g/dL (unless abnormalities are due to
histologically proven bone marrow involvement by lymphoma);
b. absolute neutrophil count (ANC) = 1.5 x 10^9/L (unless
abnormalities are due to histologically proven bone marrow involvement
by lymphoma);
c. platelet count = 100 x 10^9/L (unless abnormalities are due to
histologically proven bone marrow involvement by lymphoma);
d. total bilirubin < 1.5 x ULN (upper limit of normal) (if Gilbert-
Meulengracht syndrome is present, up to 2.0 x ULN is allowed);
e. transaminases < 2.5 x ULN;
f. serum creatinine level < 2 x ULN or calculated creatinine clearance
> 50 mL/min;
g. negative serologic or virologic markers for active or latent hepatitis
B and hepatitis C infections.
7. Sexually active males who accept to use a condom during intercourse
while taking the drug and for 12 months after stopping treatment as
they should not father a child in this period. A condom is required to be
used also by vasectomised men (as well as during intercourse with a
male partner) in order to prevent delivery of the drug via seminal fluid.
8. a) Women of child-bearing potential, defined as all women
physiologically capable of becoming pregnant, including women whose
career, lifestyle, or sexual orientation precludes intercourse with a male
partner and women whose partner have been sterilized by vasectomy or
other means, who accept to use a highly effective method of birth
control while taking study drug and for 12 months after stopping
treatment.
OR
b) Women who are considered post-menopausal and not of child bearing
potential i.e. if they have had 6 months of natural (spontaneous)
amenorrhea with an appropriate clinical profile (e.g. age appropriate,
history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy) or tubal ligation at least
six weeks ago (in the case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow up
hormone level assessment).
9. Patient has signed and dated informed consent documents according
to local guidelines.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 309
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 309

Exclusion Criteria

criteria:
1. Patient with Grade 3b (aggressive) FL or any histology other than FL
grade 1, 2 or 3a.
2. Patient with histological evidence of transformation to high grade or
diffuse large B-cell lymphoma.
3. Patient who has previously received any prior therapy for lymphoma, e.g. cytostatic or cytotoxic agents, antibodies, anti-lymphoma
vaccination, experimental treatments and radiotherapy, except who received involved field radiation 4 weeks prior to Cycle 1 Day 1, of up to two lesions that will not be used to evaluate disease progression.
4. Evidence of significant leukemic disease defined as >10 x 109 /L
circulating CD20+ lymphoma cells.
5. Patient with clinical evidence of central nervous system (CNS)
involvement by lymphoma or any evidence of spinal cord compression by
lymphoma.
6. Patient with evidence of any uncontrolled, acute or chronic active
infection (viral, bacterial, including tuberculosis or fungal).
7. Patient receiving chronic (>3 months), high dose (> 20 mg of
prednisone or > approximately 3 mg of dexamethasone per day or
equivalent doses of other steroid medications) of systemic
corticosteroids.
8. Patient with any malignancy within 5 years prior to date of
randomization, with the exception of adequately treated in situ
carcinoma of the cervix uteri, basal or squamous cell carcinoma or
nonmelanomatous skin cancer.
9. Patient with a known hypersensitivity to any of the study treatment
ingredients e.g. to recombinant human antibodies.
10. Patient with concurrent serious illnesses, uncontrolled medical
conditions, or other medical history including clinically relevant
abnormal laboratory results, which in the investigator's opinion would
be interfere with a patient's participation in the study, or with the
interpretation of study results:
a. uncontrolled neurological disease (e.g. recurrent seizures despite
existing anticonvulsant therapy);
b. neuropathy = grade 1, neuromuscular disease;
c. severe disturbance of liver function;
d. severe constipation;
e. cystitis or other ongoing infections;
f. disturbance of micturition;
g. severe chronic obstructive pulmonary disease with clinically
manifest hypoxemia;
h. uncontrolled hypertension (defined as systolic BP > 160 mm Hg or
diastolic > 100 mm Hg);
i. history of stroke or cerebral ischemia (within 6 months prior to
screening);
j. history of myocardial infarction or other clinically significant
myocardial disease (within 6 months prior to screening) or unstable
angina (= NYHA Grade II);
k. known infection with HIV or any other severe immunecompromised
state according to patient history (if required by local
regulations or clinical practice guidelines, patient may be tested during
the screening period to confirm HIV status);
l. evidence of ongoing drug or alcohol abuse within the last 6 months
before screening;
m . active tuberculosis. Patients with evidence of latent tuberculosis
as per results of the tuberculosis screening test and further follow-up
may enter the study after evaluation by an appropriate specialist and
after sufficient treatment has been initiated according to local medical
practice.
11. Patient has had major surgery, open biopsy or trauma within 4
weeks prior to date of screening (lymph node biopsy is not regarded as
major surgery), or expects the need for major surgery during the course
of study treatment.
12. Female patient who is nursing (lactating/breast-feeding), pregnant
or planning a pregnan

Study & Design

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