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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00494780
First received: June 29, 2007
Last updated: June 26, 2014
Last verified: May 2014
  Purpose

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)


Condition Intervention Phase
Lymphoma, Follicular
Drug: Ofatumumab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisolone, Prednisone or equivalent
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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).

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With the Indicated Overall Best Response (OBR) at Visit 26 (3 Months After the Last Infusion of Ofatumumab) [ Time Frame: Maximum of 23 months after the start of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Maximum of 23 months after the start of treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: Maximum of 24 months after the last infusion of Ofatumumab (Visit 33; median of 33.8 months) ] [ Designated as safety issue: No ]
    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 Frame: Followed up to 5 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: Followed up to 5 years ] [ Designated as safety issue: No ]
    PFS is defined as the time from randomization until progression or death.

  • Duration of Response [ Time Frame: Followed up to 5 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: Maximum of 24 months after the last infusion of Ofatumumab (Visit 33; median of 33.8 months) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 22 months after study start ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Visits 1 (Screening), 28 (9 months after last dose), and 33 (24 months after last dose) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Visit 1 (Screening, Week -2) and Visit 22 (Week 15) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Maximum of 6 years follow-up ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 15 (Visit 22) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 15 (Visit 22) ] [ Designated as safety issue: No ]
    AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-504) 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) [ Time Frame: Week 15 (Visit 22) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 15 (Visit 22) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 15 (Visit 22) ] [ Designated as safety issue: No ]
    Vss is defined as the volume of distribution at steady state of ofatumumab.


Enrollment: 59
Study Start Date: June 2007
Study Completion Date: September 2010
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active Comparator 1
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
Drug: Ofatumumab
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
Drug: Cyclophosphamide
Cyclophosphamide 750 mg/m2 iv for 1 day, 24-48h post-ofatumumab infusion start
Other Name: CHOP
Drug: Doxorubicin
Doxorubicin : 50mg/m2 iv for 1 day, 24-48h post-ofatumumumab infusion start
Other Name: CHOP
Drug: Vincristine
Vincristine : 1.4mg/m2 iv for 1 day, 24-48h post-ofatumumab infusion start
Other Name: CHOP
Drug: Prednisolone, Prednisone or equivalent
100mg p.o daily for 5 days, 24-48h post-ofatumumab infusion start
Other Name: CHOP
Active Comparator: Active Comparator 2
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
Drug: Ofatumumab
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
Drug: Cyclophosphamide
Cyclophosphamide 750 mg/m2 iv for 1 day, 24-48h post-ofatumumab infusion start
Other Name: CHOP
Drug: Doxorubicin
Doxorubicin : 50mg/m2 iv for 1 day, 24-48h post-ofatumumumab infusion start
Other Name: CHOP
Drug: Vincristine
Vincristine : 1.4mg/m2 iv for 1 day, 24-48h post-ofatumumab infusion start
Other Name: CHOP
Drug: Prednisolone, Prednisone or equivalent
100mg p.o daily for 5 days, 24-48h post-ofatumumab infusion start
Other Name: CHOP

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00494780

Locations
United States, New York
GSK Investigational Site
Buffalo, New York, United States, 14263
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00494780     History of Changes
Other Study ID Numbers: 111775, Hx-CD20-409, The MUNIN trial
Study First Received: June 29, 2007
Results First Received: July 28, 2011
Last Updated: June 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
CHOP (cyclophosphamide,doxorubicin,vincristine,prednisolone)
ofatumumab

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents

ClinicalTrials.gov processed this record on November 20, 2014