Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Follicular

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Anti-Infective Agents

Antibodies

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Vincristine

Prednisolone

Immunoglobulins

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Ofatumumab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

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

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

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

Cyclophosphamide 750 mg/m2 iv for 1 day, 24-48h post-ofatumumab infusion start

Doxorubicin : 50mg/m2 iv for 1 day, 24-48h post-ofatumumumab infusion start

Vincristine : 1.4mg/m2 iv for 1 day, 24-48h post-ofatumumab infusion start

100mg p.o daily for 5 days, 24-48h post-ofatumumab infusion start

Prednisolone, Prednisone or equivalent

GSK Clinical Trials

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)

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

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).

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).

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.

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 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.

PFS is defined as the time from randomization until progression or death.

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 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.

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.

HAHA are indicators of immunogenicity to ofatumumab. Blood samples were drawn from participants at Visits 1, 28, and 33 for analysis of HAHA.

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.

This is a genetic prognostic marker of FL response. The former sponsor decided to not analyze these samples; therefore, no results are presented.

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 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 is defined as the period of time required for the amount of drug in the body to be reduced by half.

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 is defined as the volume of distribution at steady state of ofatumumab.

GlaxoSmithKline

Ofatumumab was given on Day 1 and CHOP on Day 3 of each 21-day cycle, with 300 mg in Cycle 1 and 500 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.

500 mg Ofatumumab + CHOP

Ofatumumab was given on Day 1 and CHOP on Day 3 of each 21-day cycle, with 300 mg in Cycle 1 and 1000 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.

1000 mg Ofatumumab + CHOP

500 mg Ofatumumab + CHOP: Extended Follow-up

1000 mg Ofatumumab + CHOP: Extended Follow-up

Total

Baseline characteristics were collected in the Full Analysis Set (FAS), comprised of all participants who were exposed to trial drug irrespective of their compliance to the planned course of treatment.

One participant was enrolled and randomized to receive 1000 mg Ofatumumab + CHOP, but withdrew prior to initiation of therapy.

Age, Continuous

Sex: Female, Male

White

Hispanic or Latino

Race/Ethnicity, Customized

GSK Response Center

Number of Participants With Complete Remission (CR) at Visit 26

Radiologist 1

Radiologist 2

FAS. Participants were withdrawn from the study between Visits 1 and 33.

Median Percent Change From Visit 1 (Screening, Week -2) in Tumor Size at Visit 33 (24 Months After the Last Infusion of Ofatumumab)

Time to New Anti-follicular Lymphoma (FL) Therapy

Progression-Free Survival (PFS)

FAS. Only those participants with a response were analyzed.

Duration of Response

CD19+

CD20+

FAS. Only those participants who provided samples at Visit 33 were analyzed.

Percent Change From Visit 1 (Screening) in Peripheral CD19+ and CD20+ Cell Counts at Visit 33 (24 Months After the Last Infusion of Ofatumumab)

Number of Participants Who Experienced Any Adverse Event (AEs) From First Treatment to Visit 33 (24 Months After Last Infusion)

Visit 1, n=29, 29

Visit 28, n=18, 21

Visit 33, n=16, 16

FAS. Participants dropped out of the study as the study progressed.

Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Visits 1, 28, and 33

FAS. Only those participants who remained in the study at Visit 22 were analyzed.

Median Percent Change From Visit 1 (Screening) in Serum Complement (CH50) Levels at Visit 22

Responder, CR

Responder, CRu

Responder, PR

Non-Responder, SD

Non-Responder, PD

Number of Participants With the Indicated Overall Best Response (OBR) at Visit 26 (3 Months After the Last Infusion of Ofatumumab)

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

Cmax

Ctrough

FAS. Data were provided for the number of participants who had a value. Participants withdrawn during the study were not analyzed.

Cmax and Ctrough at the Sixth Infusion (Week 15, Visit 22)

AUC(0-inf), n=20, 28

AUC(0-504), n=24, 28

FAS. Data were provided for the number of participants for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.

AUC(0-inf) and AUC(0-504) After the Sixth Infusion (Week 15, Visit 22)

FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.

Half Life (t1/2) of Ofatumumab at the Sixth Infusion (Week 15, Visit 22)

CL After the Sixth Infusion (Week 15, Visit 22)

Vss at the Sixth Infusion (Week 15, Visit 22)

Ofatumumab was given on Day 1 and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) on Day 3 of each 21-day cycle, with 300 milligrams (mg) in Cycle 1 and 500 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.

Spots Global Cancer Trial Database for Ofatumumab (Humax-CD20) With CHOP (Cyclophosphamide,Doxorubicin, Vincristine, Predisolone) in Follicular Lymphoma (FL) Patients

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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