Clinical trial NCT00394836: HuMax-CD20 i(Ofatumumab) n Follicular Lymphoma (FL) Patients Refractory to Rituximab
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Follicular
Keywords: ofatumumab
rituximab
NHL
CD20
refractory
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-11-01
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria

* Patient with follicular lymphoma grade 1 - 2
* Refractory to rituximab given as monotherapy or in combination with any chemotherapy or to rituximab given as maintenance treatment following R-chemo, defined as:
* failure to achieve at least PR to rituximab given as monotherapy or in combination with any chemotherapy; or,
* disease progression while on rituximab (either given as monotherapy or in combination with any chemotherapy or during rituximab maintenance treatment following R-chemo); or,
* disease progression in responders within 6 months of the last dose of rituximab (either given as monotherapy or in combination with any chemotherapy or after rituximab maintenance treatment schedule following R-chemo)
* Tumor verified to be CD20+ positive from excisional lymph node biopsy
* CT scan in screening phase (based on local evaluation) showing:
* 2 or more clearly demarcated lesions with a largest diameter ≥ 1.5 cm, or
* 1 clearly demarcated lesion with a largest diameter ≥ 2,0 cm
* ECOG Performance Status of 0, 1, or 2
* Age ≥ 18 years
* Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out

Exclusion Criteria

* Previous autologous stem cell transplantation within 6 months
* Previous allogeneic stem cell transplantation
* More than 1 previous radio immunotherapy regimen
* Received radio immunotherapy within 3 months
* Received any Anti-cancer treatment within 4 weeks
* Received monoclonal antibodies, other than rituximab within 3 months
* Patients previously treated with anti-CD20 monoclonal antibodies, other than rituximab
* Life expectancy less than 6 months

Primary outcomes:
measure: Number of Participants With Objective Response (OR)
timeFrame: Start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32)
measure: Number of Participants Classified as Responders and Non-responders for Objective Response (OR)
timeFrame: 6-month period from the start of treatment. There was a median time of response at Month 5.5 (participants were followed for up to 24 months).
Secondary outcomes:
measure: Duration of Response
timeFrame: From start of treatment (Week 0) until Month 24
measure: Progression-Free Survival
timeFrame: From start of treatment (Week 0) until Month 24
measure: Time to Next Follicular Lymphoma (FL) Therapy
timeFrame: From start of treatment (Week 0) until Month 24
measure: Overall Survival
timeFrame: First dose (Week 0) until 5 years
measure: 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
timeFrame: Visits 1 (Week -2), 11 (Month 3), 12 (Month 6), 13 (Month 9), 14 (Month 12), 16 (Month 18), and 18 (Month 24)
measure: Percent Change From Baseline (Visit 2) in CD19+ and CD20+ Cells in Peripheral Blood at Visits 11 and 12
timeFrame: Visits 2 (Baseline), 11 (Month 3), and 12 (Month 6)
measure: Number of Participants With Conversion and no Conversion of BCL2 Positive to BCL2 Negative in Peripheral Blood
timeFrame: Screening (Visit 1) until Month 24 (Visit 18)
measure: Number of Participants Who Experienced Any Adverse Event From First Treatment (Visit 2) to Visit 18 (Month 24)
timeFrame: From first treatment (Visit 2) until Visit 18 (Month 24)
measure: Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Visits 1, 12, 13, and 14
timeFrame: Visits 1 (Screening), 12 (Month 6), 13 (Month 9), and 18 (Month 24)
measure: Complement (CH50) Levels at Visit 1 and at the End of Infusion at Visit 2
timeFrame: Visits 1 (Week -2) and 2 (Week 0)
measure: Number of Participants Classified as Responders for Fragment C Receptor (FcR) Polymorphism (Poly.)
timeFrame: From first treatment (Visit 2) until Visit 12 (Month 6)
measure: Ctrough and Cmax at the Eighth Infusion (Visit 9, Week 7)
timeFrame: Visit 9 (Week 7; up to 10 months after dose)
measure: AUC(0-inf) and AUC(0-168) After the Eighth Infusion (Visit 9, Week 7)
timeFrame: Visit 9 (Week 7; up to 10 months after dose)
measure: t1/2 After the Eighth Infusion (Visit 9, Week 7)
timeFrame: Visit 9 (Week 7; up to 10 months after dose)
measure: CL After the Eighth Infusion (Visit 9, Week 7)
timeFrame: Visit 9 (Week 7; up to 10 months after dose)
measure: Vss After the Eighth Infusion (Visit 9, Week 7)
timeFrame: Visit 9 (Week 7; to up 10 months after dose)
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Czuczman MS, Fayad L, Delwail V, Cartron G, Jacobsen E, Kuliczkowski K, Link BK, Pinter-Brown L, Radford J, Hellmann A, Gallop-Evans E, DiRienzo CG, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Schultz M, Russell CA, Hagenbeek A; 405 Study Investigators. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012 Apr 19;119(16):3698-704. doi: 10.1182/blood-2011-09-378323. Epub 2012 Mar 2.