A Phase 1/3, Randomised, Parallel-Group, Active-Controlled, Double-Blind Study to Demonstrate Equivalence of Pharmacokinetics and Noninferiority of Efficacy for CT-P10 in Comparison With Rituxan, Each Administered in Combination With Cyclophosphamide, Vincristine, and Prednisone (CVP) in Patients With Advanced Follicular Lymphoma
- Conditions
- Cancer10025320Advanced Follicular Lumphoma
- Registration Number
- NL-OMON47777
- Lead Sponsor
- CELLTRION, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
1. Patient is male or female 18 years and older.
2. Patient has histologically confirmed FL according to the World Health
Organization 2008 classification (Jaffe 2009); grades 1 to 3a based on
local laboratory review.
3. Patient has at least 1 measurable tumour mass that has not previously
been irradiated, and the mass must be:
- Nodal lesion >15mm in the longest dimension; or
- Nodal lesion >10mm to *15mm in the longest dimension and >10mm in the shortest dimension; or
- Extranodal lesion with both long and short dimensions *10mm.
4. Patient has confirmed CD20+ lymphoma, as assessed by local laboratory review.
5. Patient has Ann Arbor stage III or IV disease.
6. Patient has an Eastern Cooperative Oncology Group (ECOG)
performance status of 0 to 2 (Oken 1982).
7. For both male and female patients and their partners of childbearing
potential, patient agrees to practice total abstinence or to use one of the
following medically acceptable methods of contraception during the
course of the study and for 12 months following discontinuation of study
treatment (excluding women who are not of childbearing potential and
men who have been sterilised):
* Barrier contraceptives (male condom, female condom or diaphragm
with a spermicidal gel)
* Hormonal contraceptives (implants, injectables, combination oral
contraceptives, transdermal patches, or contraceptive rings)
* Intrauterine devices
Male or female patients and their partners who have been surgically
sterilised for less than 6 months prior to study entry must agree to use 1
medically acceptable method of contraception or practice total
abstinence. Menopausal females must have experienced their last period
more than 12 months prior to study entry (ie, when the informed
consent form [ICF] is signed) to be classified as not of childbearing
potential.
8. For both premenopausal women and women who are less than or
equal to 12 months after the onset of menopause, patient has a negative
serum pregnancy test during the Screening Period.
9. Patient has adequate bone marrow, hepatic, and renal function
reserve as evidenced by:
* Haemoglobin level of *8 g/dL
* Absolute neutrophil count (ANC) of *1500/mm3
* Platelet count of *75 000/mm3
* Total bilirubin level of *2.0 mg/dL
* Aspartate aminotransferase and alanine aminotransferase levels of *3
times the upper limit of normal (ULN) for the reference laboratory (*5 ×
ULN for the reference laboratory with known hepatic involvement by
lymphoma)
* A serum creatinine level of *1.5 × ULN for the reference laboratory, or
a calculated creatinine clearance by the Cockcroft-Gault equation
(Rostoker et al 2007) of *50 mL/min
1. Patient has received rituximab (or a rituximab proposed biosimilar product),
cyclophosphamide, or vincristine.
2. Patient has allergies or hypersensitivity to murine, chimeric, human or
humanised proteins, cyclophosphamide, vincristine, or prednisone.
3. Patient has evidence of histological transformation to high-grade or
diffuse large B-cell lymphoma.
4. Patient has known central nervous system involvement.
5. Previous treatment including chemotherapy, radiotherapy, immunotherapy, and/or surgery (except previous biopsy). However, patients who have received radiotherapy as part of the palliative therapy are eligible if the last fraction of radiotherapy was administered at least 4 weeks prior to Day 1 of Cycle 1 and patients must have recovered from all radiotherapy-related toxicities prior to randomisation.
- All doses of corticoid therapy for treatment of NHL.
- Corticoid therapy during the previous 4 weeks from Day 1 of Cycle 1 with prednisone >20mg per day for the treatment for any purpose
6. Patient has a current diagnosis of active tuberculosis (TB) defined by
chest x-ray, CT, or proper image) or other severe infections, such as sepsis, abscesses, or
opportunistic infections.
7. Patient has a known infection with human immunodeficiency virus
(HIV), hepatitis B, or hepatitis C. (Carriers of hepatitis B are not
permitted to enrol into the study.)
8. Patient has New York Heart Association class III or IV heart failure,
severe uncontrolled cardiac disease (unstable angina, clinically significant electrocardiogram abnormalities), or
myocardial infarction within the previous 6 months before the ICF is
signed.
9. Patient has any malignancy other than NHL, except adequately treated
squamous or basal cell carcinoma of the skin or cervical carcinoma in
situ, within the previous 5 years before Day 1 of Cycle 1.
10. Patient has a current or recent (within 30 days before Day 1 of Cycle 1) treatment with any other investigational medicinal product or
device.
11. Patient has uncontrolled diabetes mellitus, even after insulin
treatment.
12. Patient is pregnant or lactating. Patients who are planning to be
pregnant or to breastfeed before, during, or within 12 months after the
last infusion of study treatment are not permitted to enrol into the study.
13. Patient is taking a live, live-attenuated, or nonlive vaccine within 4
weeks before Day 1 of Cycle 1 of study treatment.
14. Patient has evidence of any other coexisting disease or medical or
psychological condition, metabolic dysfunction, physical examination
finding, or clinical laboratory finding giving reasonable suspicion of a
disease or condition that contraindicates the use of an investigational
product, or patient is a high risk for treatment complications.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary PK Endpoints:<br /><br>* AUCtau<br /><br>* CmaxSS<br /><br><br /><br>Primary efficacy endpoint:<br /><br>* Overall response rate (CR + CRu + PR) during the Core Study Period, according<br /><br>to the 1999 IWG<br /><br>criteria</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary PK Endpoints:<br /><br>* Cmax at each dose<br /><br>* Ctrough at each dose<br /><br>* Cav<br /><br>* Vd<br /><br>* CL<br /><br>* T1/2<br /><br>* Tmax<br /><br>* MRT<br /><br>* PTF<br /><br>* *z<br /><br><br /><br>Secondary Efficacy Endpoints:<br /><br>* Overall response rate (CR + PR) during the Core Study Period, according to<br /><br>the 2007 IWG criteria<br /><br>for patients who underwent PET-CT<br /><br>* Progression-free survival<br /><br>* Time to progression<br /><br>* Time to treatment failure<br /><br>* Response duration<br /><br>* Disease-free survival<br /><br>* Overall survival<br /><br><br /><br>Additional efficacy parameters:<br /><br>pharmacokinetics, pharmacodynamics and overall safety</p><br>