Back to resultsOfatumumab (Humax-CD20) With CHOP (Cyclophosphamide,Doxorubicin, Vincristine, Predisolone) in Follicular Lymphoma (FL) Patients (MUNIN)
Primary Purpose
Lymphoma, Follicular
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ofatumumab
Cyclophosphamide
Doxorubicin
Vincristine
Prednisolone, Prednisone or equivalent
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Follicular focused on measuring CHOP (cyclophosphamide,doxorubicin,vincristine,prednisolone), ofatumumab
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
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Active Comparator 1
Active Comparator 2
Arm Description
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
Outcomes
Primary Outcome Measures
Number of Participants With the Indicated Overall Best Response (OBR) at Visit 26 (3 Months After the Last Infusion of Ofatumumab)
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).
Secondary Outcome Measures
Number of Participants With Complete Remission (CR) at Visit 26
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)
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 Anti-follicular Lymphoma (FL) Therapy
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.
Progression-Free Survival (PFS)
PFS is defined as the time from randomization until progression or death.
Duration of Response
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.
Percent Change From Visit 1 (Screening) in Peripheral CD19+ and CD20+ Cell Counts at Visit 33 (24 Months After the Last Infusion of Ofatumumab)
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)
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
HAHA are indicators of immunogenicity to ofatumumab. Blood samples were drawn from participants at Visits 1, 28, and 33 for analysis of HAHA.
Median Percent Change From Visit 1 (Screening) in Serum Complement (CH50) Levels at Visit 22
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.
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
This is a genetic prognostic marker of FL response. The former sponsor decided to not analyze these samples; therefore, no results are presented.
Cmax and Ctrough at the Sixth Infusion (Week 15, Visit 22)
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)
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)
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)
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)
Vss is defined as the volume of distribution at steady state of ofatumumab.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00494780
Brief Title
Ofatumumab (Humax-CD20) With CHOP (Cyclophosphamide,Doxorubicin, Vincristine, Predisolone) in Follicular Lymphoma (FL) Patients
Acronym
MUNIN
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).
Study Type
Interventional
2. Study Status
Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
June 2007 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
September 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Follicular
Keywords
CHOP (cyclophosphamide,doxorubicin,vincristine,prednisolone), ofatumumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active Comparator 1
Arm Type
Active Comparator
Arm Description
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
Arm Title
Active Comparator 2
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Ofatumumab
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
CHOP
Intervention Description
Cyclophosphamide 750 mg/m2 iv for 1 day, 24-48h post-ofatumumab infusion start
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
CHOP
Intervention Description
Doxorubicin : 50mg/m2 iv for 1 day, 24-48h post-ofatumumumab infusion start
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
CHOP
Intervention Description
Vincristine : 1.4mg/m2 iv for 1 day, 24-48h post-ofatumumab infusion start
Intervention Type
Drug
Intervention Name(s)
Prednisolone, Prednisone or equivalent
Other Intervention Name(s)
CHOP
Intervention Description
100mg p.o daily for 5 days, 24-48h post-ofatumumab infusion start
Primary Outcome Measure Information:
Title
Number of Participants With the Indicated Overall Best Response (OBR) at Visit 26 (3 Months After the Last Infusion of Ofatumumab)
Description
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).
Time Frame
Maximum of 23 months after the start of treatment
Secondary Outcome Measure Information:
Title
Number of Participants With Complete Remission (CR) at Visit 26
Description
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.
Time Frame
Maximum of 23 months after the start of treatment
Title
Median Percent Change From Visit 1 (Screening, Week -2) in Tumor Size at Visit 33 (24 Months After the Last Infusion of Ofatumumab)
Description
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 Frame
Maximum of 24 months after the last infusion of Ofatumumab (Visit 33; median of 33.8 months)
Title
Time to New Anti-follicular Lymphoma (FL) Therapy
Description
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.
Time Frame
Followed up to 5 years
Title
Progression-Free Survival (PFS)
Description
PFS is defined as the time from randomization until progression or death.
Time Frame
Followed up to 5 years
Title
Duration of Response
Description
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.
Time Frame
Followed up to 5 years
Title
Percent Change From Visit 1 (Screening) in Peripheral CD19+ and CD20+ Cell Counts at Visit 33 (24 Months After the Last Infusion of Ofatumumab)
Description
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.
Time Frame
Maximum of 24 months after the last infusion of Ofatumumab (Visit 33; median of 33.8 months)
Title
Number of Participants Who Experienced Any Adverse Event (AEs) From First Treatment to Visit 33 (24 Months After Last Infusion)
Description
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.
Time Frame
Up to 22 months after study start
Title
Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Visits 1, 28, and 33
Description
HAHA are indicators of immunogenicity to ofatumumab. Blood samples were drawn from participants at Visits 1, 28, and 33 for analysis of HAHA.
Time Frame
Visits 1 (Screening), 28 (9 months after last dose), and 33 (24 months after last dose)
Title
Median Percent Change From Visit 1 (Screening) in Serum Complement (CH50) Levels at Visit 22
Description
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.
Time Frame
Visit 1 (Screening, Week -2) and Visit 22 (Week 15)
Title
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
Description
This is a genetic prognostic marker of FL response. The former sponsor decided to not analyze these samples; therefore, no results are presented.
Time Frame
Maximum of 6 years follow-up
Title
Cmax and Ctrough at the Sixth Infusion (Week 15, Visit 22)
Description
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]).
Time Frame
Week 15 (Visit 22)
Title
AUC(0-inf) and AUC(0-504) After the Sixth Infusion (Week 15, Visit 22)
Description
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.
Time Frame
Week 15 (Visit 22)
Title
Half Life (t1/2) of Ofatumumab at the Sixth Infusion (Week 15, Visit 22)
Description
Half life is defined as the period of time required for the amount of drug in the body to be reduced by half.
Time Frame
Week 15 (Visit 22)
Title
CL After the Sixth Infusion (Week 15, Visit 22)
Description
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.
Time Frame
Week 15 (Visit 22)
Title
Vss at the Sixth Infusion (Week 15, Visit 22)
Description
Vss is defined as the volume of distribution at steady state of ofatumumab.
Time Frame
Week 15 (Visit 22)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22409295
Citation
Czuczman MS, Hess G, Gadeberg OV, Pedersen LM, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Strange C, Windfeld K, Viardot A; 409 Study Investigators. Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma. Br J Haematol. 2012 May;157(4):438-45. doi: 10.1111/j.1365-2141.2012.09086.x. Epub 2012 Mar 13.
Results Reference
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Ofatumumab (Humax-CD20) With CHOP (Cyclophosphamide,Doxorubicin, Vincristine, Predisolone) in Follicular Lymphoma (FL) Patients
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