Ofatumumab (Humax-CD20) With CHOP (Cyclophosphamide,Doxorubicin, Vincristine, Predisolone) in Follicular Lymphoma (FL) Patients
- Conditions
- Lymphoma, Follicular
- Interventions
- Drug: Prednisolone, Prednisone or equivalent
- Registration Number
- NCT00494780
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
To investigate the efficacy in two dose regimens of ofatumumab in combination with CHOP (cyclophosphamide,doxorubicin, vincristine,prednisolone) in previously untreated patients with Follicular Lymphoma (FL)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 59
- Patient with Follicular Lymphoma (FL)
- Confirmed diagnosis of Follicular lymphoma
- 18 years or above
- Verbal and written information about the study
- No previous treatment for Follicular Lymphoma
- Clinical suspicion that the Follicular Lymphoma has transformed to aggressive lymphoma
- Several diseases such as malignancies etc.
- Screening laboratory values
- Current participation in any other interventional clinical study
- Breast feeding women or pregnant women
- Women of childbearing potential not willing to use adequate contraception
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Active Comparator 1 Prednisolone, Prednisone or equivalent Each patient will receive a total of 6 infusions with ofatumumab in combination with CHOP every 3 weeks. The first infusion will be 300mg followed by 5 infusions of 500mg Active Comparator 1 Doxorubicin Each patient will receive a total of 6 infusions with ofatumumab in combination with CHOP every 3 weeks. The first infusion will be 300mg followed by 5 infusions of 500mg Active Comparator 2 Prednisolone, Prednisone or equivalent Each patient will receive a total of 6 infusions with ofatumumab in combination with CHOP every 3 weeks. The first infusion will be 300mg followed by 5 infusions of 1000mg Active Comparator 1 Ofatumumab Each patient will receive a total of 6 infusions with ofatumumab in combination with CHOP every 3 weeks. The first infusion will be 300mg followed by 5 infusions of 500mg Active Comparator 1 Cyclophosphamide Each patient will receive a total of 6 infusions with ofatumumab in combination with CHOP every 3 weeks. The first infusion will be 300mg followed by 5 infusions of 500mg Active Comparator 1 Vincristine Each patient will receive a total of 6 infusions with ofatumumab in combination with CHOP every 3 weeks. The first infusion will be 300mg followed by 5 infusions of 500mg Active Comparator 2 Ofatumumab Each patient will receive a total of 6 infusions with ofatumumab in combination with CHOP every 3 weeks. The first infusion will be 300mg followed by 5 infusions of 1000mg Active Comparator 2 Cyclophosphamide Each patient will receive a total of 6 infusions with ofatumumab in combination with CHOP every 3 weeks. The first infusion will be 300mg followed by 5 infusions of 1000mg Active Comparator 2 Doxorubicin Each patient will receive a total of 6 infusions with ofatumumab in combination with CHOP every 3 weeks. The first infusion will be 300mg followed by 5 infusions of 1000mg Active Comparator 2 Vincristine Each patient will receive a total of 6 infusions with ofatumumab in combination with CHOP every 3 weeks. The first infusion will be 300mg followed by 5 infusions of 1000mg
- Primary Outcome Measures
Name Time Method Number of Participants With the Indicated Overall Best Response (OBR) at Visit 26 (3 Months After the Last Infusion of Ofatumumab) Maximum of 23 months after the start of treatment Based on standardized response criteria for NHL, responders included participants with CR (complete disappearance of all detectable clinical and radiographic evidence of disease), CRu (more than a 75% decrease in LN size compared to baseline), and PR (\>=50% decrease in LN size and evidence of new lesions). Non-responders included participants with stable disease (SD; \<50% decrease in LN size from baseline) and progressive disease (PD; \>=50% increase in LN size and evidence of new lesions).
- Secondary Outcome Measures
Name Time Method Median Percent Change From Visit 1 (Screening, Week -2) in Tumor Size at Visit 33 (24 Months After the Last Infusion of Ofatumumab) Maximum of 24 months after the last infusion of Ofatumumab (Visit 33; median of 33.8 months) The tumor size for a participant was computed as the sum of product of diameters (SPD) for the indicator lesions. Reduction in tumor size was calculated as percent change from Visit 1 until Visit 33, separately by radiologist 1 and radiologist 2. Percent change from Visit 1 (Screening, Week -2) = (value at Visit 33 minus value at Visit 1 divided by value at Visit 1) \* 100.
Time to New Anti-follicular Lymphoma (FL) Therapy Followed up to 5 years Time to new FL therapy is defined as the time from randomization until the time of first administration of the new FL therapy other than ofatumumab. Time to new FL therapy will be censored if participants are lost to follow-up. The censoring date in such cases will be the date of the last attended visit at which the endpoint was assessed.
Progression-Free Survival (PFS) Followed up to 5 years PFS is defined as the time from randomization until progression or death.
Duration of Response Followed up to 5 years The duration of response is defined as the time from the initial response (the first visit at which response was observed) to progression or death.
Percent Change From Visit 1 (Screening) in Peripheral CD19+ and CD20+ Cell Counts at Visit 33 (24 Months After the Last Infusion of Ofatumumab) Maximum of 24 months after the last infusion of Ofatumumab (Visit 33; median of 33.8 months) The peripheral blood for each participant was collected and analyzed for CD19+ and CD20+ cell counts. CD19+ and CD20+ are B-cell types which are used as an index of a participant's response to treatment.
Number of Participants Who Experienced Any Adverse Event (AEs) From First Treatment to Visit 33 (24 Months After Last Infusion) Up to 22 months after study start An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. A list of AEs experienced in the study with a frequency threshold of 5% can be found in the AE section.
Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Visits 1, 28, and 33 Visits 1 (Screening), 28 (9 months after last dose), and 33 (24 months after last dose) HAHA are indicators of immunogenicity to ofatumumab. Blood samples were drawn from participants at Visits 1, 28, and 33 for analysis of HAHA.
Median Percent Change From Visit 1 (Screening) in Serum Complement (CH50) Levels at Visit 22 Visit 1 (Screening, Week -2) and Visit 22 (Week 15) The peripheral blood for each participant was collected and analyzed for serum complement CH50 levels. Cluster of Differentiation index 50 (CD50) is a human gene which is used as an index of immune response. CD50Percent change from Visit 1 (Screening, Week -2) = (value at Visit 22 minus value at Visit 1 divided by value at Visit 1) \* 100.
Number of Participants Who Had a Conversion of BCL-2 t(14;18)-Positive to Negative by Polymerase Chain Reaction (PCR) in Peripheral Blood and Bone Marrow Aspirate and Its Durability Post-therapy Maximum of 6 years follow-up This is a genetic prognostic marker of FL response. The former sponsor decided to not analyze these samples; therefore, no results are presented.
Cmax and Ctrough at the Sixth Infusion (Week 15, Visit 22) Week 15 (Visit 22) Cmax is defined as the maximum concentration of drug in plasma samples. Ctrough is defined as the trough plasma concentration (measured concentration at the end of a dosing interval \[taken directly before next administration\]).
AUC(0-inf) and AUC(0-504) After the Sixth Infusion (Week 15, Visit 22) Week 15 (Visit 22) AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-504) is AUC from the start of infusion to 504 hours after the start of the infusion; AUC(0-inf) is AUC from the start of infusion extrapolated to infinity.
Half Life (t1/2) of Ofatumumab at the Sixth Infusion (Week 15, Visit 22) Week 15 (Visit 22) Half life is defined as the period of time required for the amount of drug in the body to be reduced by half.
CL After the Sixth Infusion (Week 15, Visit 22) Week 15 (Visit 22) CL is the clearance of drug from plasma, which is defined as the volume of plasma from which the drug is cleared per unit time.
Vss at the Sixth Infusion (Week 15, Visit 22) Week 15 (Visit 22) Vss is defined as the volume of distribution at steady state of ofatumumab.
Number of Participants With Complete Remission (CR) at Visit 26 Maximum of 23 months after the start of treatment Participants were evaluated for response by an Independent Endpoint Review Committee in accordance with the standardized response criteria for NHL. Participants with CR were defined as those with the complete disappearance of all detectable clinical and radiographic evidence of disease.
Trial Locations
- Locations (1)
GSK Investigational Site
🇺🇸Buffalo, New York, United States