Ofatumumab in Patients With Relapsed/Progressive Diffused Large B-Cell Lymphoma (DLBCL) Ineligible for or Relapse/Progression After Transplant - Full Text View

Purpose

The purpose of this trial is to determine the effect of ofatumumab in patients with Diffused Large B-Cell Lymphoma (DLBCL) ineligible for transplant or relapsed after autologous transplant

Condition	Intervention	Phase
Diffuse Large B Cell Lymphoma (DLBCL)	Drug: Ofatumumab	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-label, Single-arm. Multi-center Phase 2 Trial With Ofatumumab in Patients With Relapsed/Progressive Diffuse Large B-Cell Lymphoma (DLBCL) Ineligible for Transplant or Relapse/Progression After Autologous Transplant

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Ofatumumab

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Number of Participants With Objective Response [ Time Frame: 6-month period from start of treatment (up to Week 24). Participants were followed up for an average of 2.8 months. ] [ Designated as safety issue: No ]
Objective response of ofatumumab treatment was assessed according to the "revised response criteria for malignant lymphoma." Participants with objective response were defined as responders with complete remission (CR) or partial remission (PR) of disease. CR is defined as the disappearance of all evidence of disease, and PR is defined as the regression of measurable disease with no new sites of disease.
Number of Participants Classified as Responders and Non-responders for Objective Response [ Time Frame: 6-month period from start of treatment (up to Week 24). Participants were followed up for an average of 2.8 months. ] [ Designated as safety issue: No ]
According to the "revised response criteria for malignant lymphoma," responders included participants with CR and PR, and non-responders included participants with stable disease (SD) and progressive disease (PD). Participants not evaluable (NE) were also considered to be non-responders. PD is defined as any new lesion or an increase by more than or equal to 50% of previously involved sites from baseline. SD is defined as failure to attain CR, PR, or PD.

Secondary Outcome Measures:

Duration of Response [ Time Frame: From date of randomization of the first participant to when the last participant completed the 6-month follow up visit. Participants were followed up for an average of 2.8 months. ] [ Designated as safety issue: No ]
The duration of response was defined as the time from the initial response (CR or PR) to the time of relapse, progression, or death. If the participant was lost to follow-up, the endpoint was censored, and the censoring date was the date of the last attended visit at which the endpoint was assessed. However, in cases in which the participant was withdrawn due to ineffective therapy, the withdrawal date was considered as the relapse or progression date.
Progression-free Survival (PFS) [ Time Frame: From date of randomization of the first participant to when the last participant completed the 6-month follow up visit. Participants were followed up for an average of 2.8 months. ] [ Designated as safety issue: No ]
PFS was defined as the time from treatment start until progression or death.
Time to Next Diffuse Large B-Cell Lymphoma (DLBCL) Therapy [ Time Frame: From date of randomization of the first participant to when the last participant completed the 6-month follow up visit. Participants were followed up for an average of 2.8 months. ] [ Designated as safety issue: No ]
Time to next DLBCL therapy was defined as the time from the first infusion date to the time of the first administration of the next DLBCL treatment other than ofatumumab. If the participants were lost to follow-up, the endpoint was censored, and the censoring date was the date of the last attended visit at which the endpoint was assessed. However, in cases in which the participant was withdrawn due to ineffective therapy, the withdrawal date was to be considered as the next DLBCL therapy date.
Overall Survival (OS) [ Time Frame: Participants were followed up for an average of 2.8 months ] [ Designated as safety issue: No ]
Overall survival is defined as the time from first infusion to death. It is not possible to analyze data for this outcome measure at this time due to the short follow up period. Data will be analyzed and reported when all participants have completed the trial.
Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Screening and at Visits 12, 13, 14, and 18 [ Time Frame: Screening visit (=<14 days before treatment start), Visit 12 (Month 6), Visit 13 (Month 9), Visit 14 (Month 12), and Visit 18 (Month 24) ] [ Designated as safety issue: No ]
HAHA are indicators of immune response to ofatumumab. Blood samples were collected from participants at Visits 1, 12, 13, 14, and 18 and analyzed in batches. The number of participants with positive results at each visit is reported.
Median Percent Change From Baseline in CD45+CD19+ and CD45+CD20+ Cells in the Peripheral Blood at the Indicated Visits [ Time Frame: Baseline and Visit 10 (Week 8), Visit 11 (Week 11), Visit 12 (Month 6), Visit 13 (Month 9), Visit 14 (Month 12), Visit 15 (Month 15), Visit 16 (Month 18), Visit 17 (Month 21), Visit 18 (Month 24) ] [ Designated as safety issue: No ]
Malignant B cells (CD45+CD19+ and CD45+CD20+) were measured in peripheral blood samples by flow cytometry. Percent change from Baseline = (value at the indicated visits minus the value at Baseline divided by the value at Baseline) * 100.
Number of Participants Who Experienced at Least One Adverse Event (AE) [ Time Frame: Participants were followed up for an average of 2.8 months from start of treatment. ] [ Designated as safety issue: No ]
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. The protocol-defined AE reporting period was from the first infusion (Visit 2/Week 0) to Visit 18 (Month 24 of follow-up) or time of withdrawal (treatment and follow-up).
Percent Change From Screening in Complement (CH50) Levels [ Time Frame: Screening and post-baseline visits (last visit was to occur 24 months post first dose) ] [ Designated as safety issue: No ]
CH50 was mistakenly registered as an outcome measure with the protocol record. Samples were not collected, and no analysis will take place. Thus, no data will be reported for this outcome measure.
AUC(0-inf) and AUC(0-168) for Ofatumumab at the Eighth Infusion [ Time Frame: Visit 9 (Week 7; up to 11 months after last dose) ] [ Designated as safety issue: No ]
AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-168) is the AUC from the start of infusion to 168 hours after the start of the infusion; AUC(0-inf) is the AUC from the start of infusion extrapolated to infinity.
Cmax and Ctrough for Ofatumumab at the First and Eighth Infusions [ Time Frame: Visit 2 (Week 0) and Visit 9 (Week 7) ] [ Designated as safety issue: No ]
Cmax is defined as the maximum concentration of drug in serum samples. Ctrough is defined as the minimum observed concentration prior to the start of the next dose. No drug is present prior to the first infusion; therefore, there are no Ctrough results for the first dose.
Half-life (T1/2) for Ofatumumab at the Eighth Infusion [ Time Frame: Visit 9 (Week 7; up to 11 months after last dose) ] [ Designated as safety issue: No ]
t1/2 is defined as terminal half-life and is the time required for the amount of drug in the body to decrease by half.
Clearance (CL) of Ofatumumab at the Eighth Infusion [ Time Frame: Visit 9 (Week 7; up to 11 months after last dose) ] [ Designated as safety issue: No ]
CL is the clearance of drug from serum, which is defined as the volume of serum from which the drug is cleared per unit time.
Volume of Distribution at Steady State (Vss) of Ofatumumab at the Eighth Infusion [ Time Frame: Visit 9 (Week 7; up to 11 months after the last dose) ] [ Designated as safety issue: No ]
Vss is the volume of distribution at steady state of ofatumumab.

Enrollment:	81
Study Start Date:	December 2007
Estimated Study Completion Date:	August 2014
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: Ofatumumab 8 weekly intra-venous (I.V.) infusions, 1x300 mg and 7x1000mg

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with DLBCL

and relapse after complete remission or disease progression after partial remission who are ineligible for autologous stem cell transplantation
and relapse after complete remission or disease progression after partial remission following autologous stem cell transplantation.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00622388

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00622388 History of Changes
Other Study ID Numbers:	111776, GEN415
Study First Received:	February 13, 2008
Results First Received:	August 4, 2011
Last Updated:	July 19, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms

Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on May 16, 2013