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: 20.0Level: 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: 20.0Level: 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-PL
- Lead Sponsor
- HEXAL AG (a Sandoz company)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 618
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Patient with previously untreated advanced stage, CD20-positive FL:
a. Ann Arbor classification stage III/IV; and
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 2D-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 ULNor calculated creatinine clearance › 50 mL/min;
g. negative serology 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
Patients eligible for this study must not meet any of the following 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, radiotherapy, antibodies, anti-lymphoma vaccination, experimental treatments), 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 doses (> 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 likely to 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 (dyspnea > grade 1);
h. uncontrolled hypertension (definied as systolic BP > 160 mm Hg or diastolic > 100 mm Hg);
i. history of stroke or cerebral ischemia (within 6 months prior to randomization);
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 immune-compromised 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 result of the tuberculosis screening test and futher 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 su
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method