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

Lymphoma, Large-Cell, Diffuse Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00622388
• Other study ID #: 111776
• Secondary ID: GEN415
• Status: Completed
• Phase: Phase 2
• First received: February 13, 2008
• Last updated: July 2, 2015
• Start date: December 2007
• Est. completion date: August 2014

Study information

• Verified date: January 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: August 2014
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Diffuse

Intervention

Drug:
• Ofatumumab
8 weekly intra-venous (i.v.) infusions, 1 x 300mg and 7 x 1000mg

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	London

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Objective Response	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.	6-month period from start of treatment (up to Week 24)	No
Primary	Number of Participants Classified as Responders and Non-responders for Objective Response	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.	6-month period from start of treatment (up to Week 24)	No
Secondary	Duration of Response	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.	From date of start of treatment to 2 years or withdrawal	No
Secondary	Progression-free Survival (PFS)	PFS was defined as the time from treatment start until progression or death.	From date of start of treatment to 2 years or withdrawal	No
Secondary	Time to Next Diffuse Large B-Cell Lymphoma (DLBCL) Therapy	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.	From date of start of treatment to 5 years or withdrawal	No
Secondary	Overall Survival (OS)	Overall survival is defined as the time from first infusion to death. Overall survival was a secondary endpoint in the study. However, since many participants withdrew from the study after developing disease progression overall survival could not be reliably estimated.	From date of start of treatment to 5 years or withdrawal	No
Secondary	Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Screening and at Visits 12, 13, 14, and 18	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.	Screening visit (=<14 days before treatment start), Visit 12 (Month 6), Visit 13 (Month 9), Visit 14 (Month 12), and Visit 18 (Month 24)	No
Secondary	Median Percent Change From Baseline in CD45+CD19+ and CD45+CD20+ Cells in the Peripheral Blood at the Indicated Visits	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.	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), Visit 19 (Month 30), Visit 20 (Month 36)	No
Secondary	Number of Participants Who Experienced at Least One Adverse Event (AE)	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).	Time frame is from date of start of treatment to 2 years or withdrawal	No
Secondary	Percent Change From Screening in Complement (CH50) Levels	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.	Screening and post-baseline visits (last visit was to occur 24 months post first dose)	No
Secondary	AUC(0-inf) and AUC(0-168) for Ofatumumab at the Eighth Infusion	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.	Visit 9 (Week 7; up to 11 months after last dose)	No
Secondary	Cmax and Ctrough for Ofatumumab at the First and Eighth Infusions	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.	Visit 2 (Week 0) and Visit 9 (Week 7)	No
Secondary	Half-life (T1/2) for Ofatumumab at the Eighth Infusion	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.	Visit 9 (Week 7; up to 11 months after last dose)	No
Secondary	Clearance (CL) of Ofatumumab at the Eighth Infusion	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.	Visit 9 (Week 7; up to 11 months after last dose)	No
Secondary	Volume of Distribution at Steady State (Vss) of Ofatumumab at the Eighth Infusion	Vss is the volume of distribution at steady state of ofatumumab.	Visit 9 (Week 7; up to 11 months after the last dose)	No