Ofatumumab (Humax-CD20) With CHOP (Cyclophosphamide,Doxorubicin, Vincristine, Predisolone) in Follicular Lymphoma (FL) Patients | RxWiki

Ofatumumab (Humax-CD20) With CHOP (Cyclophosphamide,Doxorubicin, Vincristine, Predisolone) in Follicular Lymphoma (FL) Patients

Overview[ - collapse ][ - ]

Purpose	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)
Condition	Lymphoma, Follicular
Intervention	Drug: Ofatumumab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisolone, Prednisone or equivalent
Phase	Phase 2
Sponsor	GlaxoSmithKline
Responsible Party	GlaxoSmithKline
ClinicalTrials.gov Identifier	NCT00494780
First Received	June 29, 2007
Last Updated	March 13, 2014
Last verified	March 2014

Tracking Information[ + expand ][ + ]

First Received Date	June 29, 2007
Last Updated Date	March 13, 2014
Start Date	June 2007
Estimated Primary Completion Date	September 2010
Current Primary Outcome Measures	Number of Participants Classified as Responders at Visit 26 (3 Months After Last Infusion of Ofatumumab) [Time Frame: Maximum of 23 months after the start of treatment] [Designated as safety issue: No]An Independent Review Committee (IRC) assessed overall best response based on standardized response criteria for non-Hodgkin's Lymphomas (NHL) and classified the participants as responders and non-responders. Responders included participants with complete remission (CR; complete disappearance of all detectable clinical and radiographic evidence of disease), complete remission unconfirmed (CRu; more than a 75% decrease in lymph node [LN] size compared to baseline), and partial response (PR; >=50% decrease in LN size and evidence of new lesions). Number of Participants With the Indicated Overall Best Response (OBR) at Visit 26 (3 Months After the Last Infusion of Ofatumumab) [Time Frame: Maximum of 23 months after the start of treatment] [Designated as safety issue: No]Based on standardized response criteria for NHL, responders included participants with CR, CRu, and PR. 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).
Current Secondary Outcome Measures	Number of Participants With Complete Remission (CR) at Visit 26 [Time Frame: Maximum of 23 months after the start of treatment] [Designated as safety issue: No]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. Median Percent Change From Visit 1 (Screening, Week -2) in Tumor Size at Visit 33 (24 Months After the Last Infusion of Ofatumumab) [Time Frame: Maximum of 24 months after the last infusion of Ofatumumab (Visit 33; median of 33.8 months)] [Designated as safety issue: No]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. Progression-Free Survival (PFS) [Time Frame: Followed up for up to 6 years] [Designated as safety issue: No]PFS is defined as the time from randomization until progression or death. The study is ongoing at the time of results reporting; results will be reported after study completion. Time to Next Anti-follicular Lymphoma (FL) Therapy [Time Frame: Followed up for up to 6 years] [Designated as safety issue: No]Time to next FL therapy is defined as the time from randomization until the time of first administration of the next FL therapy other than ofatumumab. Time to next 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. Because this study is ongoing, there are insufficient data to determine time to next FL therapy at this time. Duration of Response [Time Frame: Followed up for up to 6 years] [Designated as safety issue: No]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. The study is ongoing at the time of results reporting; results will be reported after study completion. Quartile and median survival times will be derived and presented together with two-sided 95% confidence intervals. Percent Change From Visit 1 (Screening) in Peripheral CD19+ and CD20+ Cell Counts at Visit 33 (24 Months After the Last Infusion of Ofatumuab) [Time Frame: Maximum of 24 months after the last infusion of Ofatumuab (Visit 33; median of 33.8 months)] [Designated as safety issue: No]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) [Time Frame: Up to 22 months after study start] [Designated as safety issue: Yes]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 [Time Frame: Visits 1 (Screening), 28 (9 months after last dose), and 33 (24 months after last dose)] [Designated as safety issue: No]HAHA are indicators of immunogenicity to ofatumumab. Blood samples were drawn from participants at Visits 1, 28, and 33 for analysis of HAHA. Analysis of HAHA samples was done in batches. The study is ongoing at the time of results reporting; results will be reported after study completion. Median Percent Change From Visit 1 (Screening) in Serum Complement (CH50) Levels at Visit 22 [Time Frame: Visit 1 (Screening, Week -2) and Visit 22 (Week 15)] [Designated as safety issue: No]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. Conversion of BCL-2 t(14;18)-Positivity by Polymerase Chain Reaction (PCR) in Peripheral Blood and Bone Marrow Aspirate and Its Durability Post-therapy [Time Frame: Maximum of 6 years follow-up] [Designated as safety issue: No]This is a genetic prognostic marker of FL response. The study is ongoing at the time of results reporting; results will be reported after study completion. Cmax and Ctrough at the Sixth Infusion (Week 15, Visit 22) [Time Frame: Week 15 (Visit 22)] [Designated as safety issue: No]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) [Time Frame: Week 15 (Visit 22)] [Designated as safety issue: No]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) [Time Frame: Week 15 (Visit 22)] [Designated as safety issue: No]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) [Time Frame: Week 15 (Visit 22)] [Designated as safety issue: No]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) [Time Frame: Week 15 (Visit 22)] [Designated as safety issue: No]Vss is defined as the volume of distribution at steady state of ofatumumab.

Descriptive Information[ + expand ][ + ]

Brief Title	Ofatumumab (Humax-CD20) With CHOP (Cyclophosphamide,Doxorubicin, Vincristine, Predisolone) in Follicular Lymphoma (FL) Patients
Official Title	An Open-labeled, Randomized, Two-dose, Parallel Group Trial of Ofatumumab, a Fully Human Monoclonal Anti-CD20 Antibody, in Combination With CHOP, in Patients With Previously Untreated Follicular Lymphoma (FL).
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 Provided
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Lymphoma, Follicular
Intervention	Drug: Ofatumumab ofatumumab 300mg, 500mg or 1000mg should be diluted into 1000mL pyrogen free saline and administered as an IV infusion.Duration of infusion will be approximately 4 hours.Infusions should be given every 3 weeks until a total of 6 infusions has been given Drug: Cyclophosphamide Cyclophosphamide 750 mg/m2 iv for 1 day, 24-48h post-ofatumumab infusion start Other Names: CHOPDrug: Doxorubicin Doxorubicin : 50mg/m2 iv for 1 day, 24-48h post-ofatumumumab infusion start Other Names: CHOPDrug: Vincristine Vincristine : 1.4mg/m2 iv for 1 day, 24-48h post-ofatumumab infusion start Other Names: CHOPDrug: Prednisolone, Prednisone or equivalent 100mg p.o daily for 5 days, 24-48h post-ofatumumab infusion start Other Names: CHOP
Study Arm (s)	Active Comparator: Active Comparator 1 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: Active Comparator 2 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

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	59
Estimated Completion Date	September 2010
Estimated Primary Completion Date	April 2009
Eligibility Criteria	Inclusion Criteria: - Patient with Follicular Lymphoma (FL) - Confirmed diagnosis of Follicular lymphoma - 18 years or above - Verbal and written information about the study Exclusion Criteria: - 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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT00494780
Other Study ID Numbers	111775
Has Data Monitoring Committee	Yes
Information Provided By	GlaxoSmithKline
Study Sponsor	GlaxoSmithKline
Collaborators	Not Provided
Investigators	Study Director: GSK Clinical Trials GlaxoSmithKline
Verification Date	March 2014

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