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

Antibodies

Rituximab

Immunoglobulins

Ofatumumab

Antibodies, Monoclonal

Immunologic Factors

Eight weekly infusions of ofatumumab. The first infusion of 300mg ofatumunab

followed by 7 weekly infusions of 1000mg ofatumumab

GSK Clinical Trials

A Single-Arm, International, Multi-Center Trial of HuMax-CD20 (Ofatumumab), a Fully Human Monoclonal Anti-CD20 Antibody, in Patients With Follicular Lymphoma Who Are Refractory to Rituximab as Monotherapy or in Combination With Chemotherapy

Patients in the study will be randomized into two dose groups. Patients in each dose group will receive one infusion of 300 mg of HuMax-CD20 followed by 7 weekly infusions of either 500 or 1000 mg of HuMax-CD20. Disease status will be assessed every 3 months until month 24.

HuMax-CD20 i(Ofatumumab) n Follicular Lymphoma (FL) Patients Refractory to Rituximab

A Single-arm, International, Multi-center Trial of HuMax-CD20, a Fully Human Monoclonal Anti-CD20 Antibody, in Patients With Follicular Lymphoma Who Are Refractory to Rituximab as Monotherapy or in Combination With Chemotherapy

OR was assessed by an Independent endpoints Review Committee (IRC) according to the standardized response criteria for Non-Hodgkin's lymphoma. Participants with Complete Response (CR; complete disappearance of all detectable disease), Complete Response unconfirmed (CRu; any residual lymph node/nodal mass \>1.5 centimeters \[cm\] in its longest transverse diameter that regressed \>75% compared to baseline), or Partial Response (PR; \>=50% decrease in the sum of the product of diameters of indicator lesions) were defined as responders for OR.

Based on OR over a 6-month period from start of treatment, participants were classified as responders/non-responders as follows: participants with CR, CRu, or PR were classified as responders, whereas participants with Stable Disease (SD; achieving less than PR but not consistent with PD), Progressive Disease (PD; 50% increase from nadir in the products of the greatest perpendicular diameters of any previously identified node or appearance of any new node \>1 cm), or Not Evaluable (NE) participants were classified as non-responders.

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. For participants who were lost to follow-up, duration of response was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate duration of response.

Progression-free survival (PFS) is defined as the time from randomization until the first radiologically or clinically documented evidence of progression or death due to any cause, if sooner. For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS.

Time to next FL (anti-lymphoma) therapy is defined as the time from randomization until the time of first administration of the next anti-lymphoma therapy other than ofatumumab. For participants who were lost to follow-up, the time was censored at the date of the last attended visit at which the endpoint was assessed.

Overall survival is defined as the time from randomization until death. For participants who are lost to follow-up, overall survival will be censored at the date of the last attended visit at which the endpoint was assessed.

Tumor size was measured by computed tomography (CT) scan and was computed as the sum of product of diameters (SPD) for the indicator lesions. CT scans with contrast of the neck, thorax, abdomen, and pelvis were performed at Screening and during the follow-up period (Month 3, 6, 9, 12, 18, and 24). The change in tumor size from Screening (Visit 1) was presented per Radiologist 1 (R1) and Radiologist 2 (R2). Percent change from Screening (Visit 1, Week -2) = (value at Visits 11, 12, 13, 14, 16, and 18 minus the value at Visit 1 divided by the value at Visit 1) \* 100.

CD19 and CD20 are proteins found on the cell surface of B cells, and they can be detected in peripheral blood by flow cytometry. Flow cytometry of peripheral blood was performed for immediate analysis of cells with cluster of differentiation 19 (CD19+) and CD20+. The analysis will be done until a value is reached that is in the normal range. Percent change from Baseline (Visit 2) = (value at Visits 11 and 12 minus the value at Visit 2 divided by the value at Visit 2) \* 100.

B-cell lymphoma 2 (BCL2) is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. BCL2 mitochondrial ribonucleic acid (mRNA) was measured by polymerase chain reaction (PCR) from peripheral blood. Participants who had no post-screening data were categorized as "Missing."

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. A list of AEs experienced in the study at a frequency threshold of 5% can be found in the AE section.

HAHA are indicators of immunogenicity to ofatumumab. Blood samples were withdrawn from participants at Visits 1, 12, 13, and 18 for analysis of HAHA. Analysis of HAHA was done in batches.

Blood samples were drawn from participants at Visits 1 and 2 for analysis of complement (CH50) levels. Analysis of CH50 was done in batches, and CH50 levels were measured two hours after the end of study medication infusion. Percent change from Screening (Visit 1, Week -2) = (value at Visit 2 minus the value at Visit 1 divided by the value at Visit 1) \* 100.

FcR poly. affect the affinity with which FcRs interact with immunoglobulin molecules and are prognostic factors that are indicative of altered responsiveness to treatment and/or survival. A blood sample was drawn at Visit 1 for analysis (done in batches of several samples) of FcR poly. (Fcgamma RIIIa Valine/Phenylalanine genotypes \[TT=thymidine/thymidine, TG=thymidine/guanine, GG=guanine/guanine\] and Fcgamma RIIa Arginine/Histidine genotypes \[AA=adenine/adenine, AG=adenine/guanine, GG=guanine/guanine\]). Responders must have met the criteria for CR, CRu, or PR at either Month 3 or Month 6. Fc receptor polymorphisms and C1qA-276 results are not included in this results summary.

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 \[taken directly before the start of the next infusion\]).

AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-168) is AUC from the start of infusion to 168 hours after the start of the infusion; AUC(0-inf) is AUC from the start of infusion extrapolated to infinity.

t1/2 is defined as terminal half-life, which is the time required for the amount of the drug in the body to decrease by half.

CL is the clearance of drug from plasma, which is defined as the volume of plasma from which drug is removed per unit time.

Vss is the volume of distribution at steady state of ofatumumab.

GlaxoSmithKline

During the Extended Follow-up Phase, from 2 years to 5 years after first treatment, only serious adverse events (SAEs) were collected; no non-serious AEs were collected during this period.

Ofatumumab intravenous (iv) infusion initiated at 300 milligrams (mg), followed by an infusion of 500 mg administered once weekly for 7 infusions

Ofatumumab 500 mg

Ofatumumab iv infusion initiated at 300 mg, followed by an infusion of 1000 mg administered once weekly for 7 infusions

Ofatumumab 1000 mg

Ofatumumab intravenous (iv) infusion initiated at 300 milligrams (mg), followed by an infusion of 500 mg administered once weekly for 7 infusions. In the extended follow-up phase of the study, participants were followed only for survival status for up to 5 years and new follicular lymphoma (FL) treatment. Time to the next FL treatment analysis included participants which received new FL treatment during extended follow-up.

Ofatumumab 500 mg: Extended Follow-up Phase

Ofatumumab iv infusion initiated at 300 mg, followed by an infusion of 1000 mg administered once weekly for 7 infusions. In the extended follow-up phase of the study, participants were followed only for survival status for up to 5 years and new Follicular lymphoma (FL) treatment. Time to the next FL treatment analysis included participants which received new FL treatment during extended follow-up.

Ofatumumab 1000 mg: Extended Follow-up Phase

Total

Age, Continuous

Sex: Female, Male

Asian

Black or African American

Hispanic or Latino

White

Reunion Island Native

Race/Ethnicity, Customized

GSK Response Center

Full Analysis Set (FAS): all participants who were exposed to study drug irrespective of their compliance to the planned course of treatment

Number of Participants With Objective Response (OR)

Responders with CR

Responders with CRu

Responders with PR

Non-responders with SD

Non-responders with PD

Non-responders with NE

Number of Participants Classified as Responders and Non-responders for Objective Response (OR)

FAS. Only those participants classified as responders were analyzed.

Duration of Response

Progression-Free Survival

Time to Next Follicular Lymphoma (FL) Therapy

FAS. As of the time of data cut-off, data for Overall Survival was not estimable because too few deaths have occurred at the time of study completion.

Overall Survival

Visit 11 (Month 3), R1, n=14, 47

Visit 11 (Month 3), R2, n=15, 47

Visit 12 (Month 6), R1, n=7, 34

Visit 12 (Month 6), R2, n=7, 33

Visit 13 (Month 9), R1, n=6, 25

Visit 13 (Month 9), R2, n=6, 26

Visit 14 (Month 12), R1, n=4, 17

Visit 14 (Month 12), R2, n=4, 18

Visit 16 (Month 18), R1, n=3, 12

Visit 16 (Month 18), R2, n=3, 12

Visit 18 (Month 24), R1, n=2, 8

Visit 18 (Month 24), R2, n=2, 8

FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Percent Change From Screening (Visit 1) in Tumor Size as Assessed by Radiologist 1 (R1) and Radiologist 2 (R2) at Months 3, 6, 9, 12, 18, and 24

Visit 11 (Month 3), CD19+, n=15, 42

Visit 11 (Month 3), CD20+, n=15, 45

Visit 12 (Month 6), CD19+, n=8, 32

Visit 12 (Month 6), CD20+, n=8, 34

Percent Change From Baseline (Visit 2) in CD19+ and CD20+ Cells in Peripheral Blood at Visits 11 and 12

Participants converted from positive to negative

Participants not converted

Missing

FAS. Only those participants who were BCL2 positive at Screening were analyzed.

Number of Participants With Conversion and no Conversion of BCL2 Positive to BCL2 Negative in Peripheral Blood

Number of Participants Who Experienced Any Adverse Event From First Treatment (Visit 2) to Visit 18 (Month 24)

Visit 1 (Week -2), n=30, 85

Visit 12 (Month 6), n=8, 33

Visit 13 (Month 9), n=7, 24

Visit 14 (Month 12), n=3, 11

Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Visits 1, 12, 13, and 14

Visit 2 (Week 0), n=30, 84

Complement (CH50) Levels at Visit 1 and at the End of Infusion at Visit 2

Fc Gamma IIa Genotype = AA, n=4, 9

Fc Gamma IIa Genotype = AG, n=11, 37

Fc Gamma IIa Genotype = GG, n=3, 12

Fc Gamma IIIa Genotype = TT, n=5, 31

Fc Gamma IIIa Genotype = TG, n=11, 23

Fc Gamma IIIa Genotype = GG, n=2, 4

Number of Participants Classified as Responders for Fragment C Receptor (FcR) Polymorphism (Poly.)

Ctrough, n=24, 78

Cmax, n=23, 78

FAS. Data were provided for the number of participants who had a value. Cmax was not reported for one participant due to missing data. Participants withdrawn during the study were not analyzed. Interim results; data as of 28 April 2009.

Ctrough and Cmax at the Eighth Infusion (Visit 9, Week 7)

AUC(0-inf), n=12, 55

AUC(0-168), n=19, 75

FAS. Data were provided for the number of participants for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed. Interim results; data as of 28 April 2009.

AUC(0-inf) and AUC(0-168) After the Eighth Infusion (Visit 9, Week 7)

t1/2 After the Eighth Infusion (Visit 9, Week 7)

CL After the Eighth Infusion (Visit 9, Week 7)

FAS. Data were provided for the number of participants for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed. Interim results; data of 28 April 2009.

Spots Global Cancer Trial Database for HuMax-CD20 i(Ofatumumab) n Follicular Lymphoma (FL) Patients Refractory to Rituximab

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial