Last updated: 11/03/2018 12:12:49
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.

Ofatumumab with fludarabine and cyclophosphamide in B-CLL patientsBIFROST

GSK study ID
111774
See study documents
Clinicaltrials.gov ID
NCT00410163
See results summary
EudraCT ID
2007-000243-10
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: An open-labeled, randomized, two-dose, parallel group trial of ofatumumab, a fully human monoclonal anti-CD20 antibody, in combination with fludarabine and cyclophosphamide, in patients with previously untreated B-cell CLL
Trial description: To investigate the safety and efficacy of two dose regimes of ofatumumab in combination with chemotherapy in previously untreated patients with B-CLL
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:

Number of participants (par.) with Complete Remission (CR), measured from start of treatment until 3 months after last infusion

Timeframe: Start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32)

Number of participants (par.) who were classified as responders and non-responders

Timeframe: From start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32)

Secondary outcomes:

Duration of Response

Timeframe: From time of initial response to disease progression or death, whichever came first, assessed over 2 years

Progression-Free Survival

Timeframe: From time of randomization to first documented evidence of disease progression or death due to any cause, whichever came first, assessed over 2 years

Time to next anti-chronic lymphocytic leukemia (CLL) therapy or death

Timeframe: From time of randomization to first administration of next anti-CLL therapy other than ofatumumab or death, assessed over 5 years

Median percent change in tumor size from Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37

Timeframe: Baseline Visit 2 (Week [Wk] 0); Visits 9 (Wk 4), 21 (Wk 12), 25 (Wk 16), 29 (Wk 20), 33 (Month [M] 1 after start of last infusion [LI]), 34 (M 3 after start of LI), 35 (M 6 after start of LI), 36 (M 9 after start of LI), and 37 (M 12 after start of L

Median percent change in CD5+CD19+ and CD5+CD20+ cells in peripheral blood from onset of course 3 throughout follow-up (FU) compared to screening

Timeframe: Baseline Visit 2 (Week [Wk] 0); Visits 15 (Wk 8), 21 (Wk 12), 25 (Wk 16), 29 (Wk 20), 33 (Month [M] 1 after start of last infusion [LI]), 34 (M 3 after start of LI)

Number of participants who experienced any adverse event from first treatment (Visit 2) to Visit 43 (Month 60)

Timeframe: From first treatment (Visit 2) up to Visit 43 (Month 60)

Number of participants with positive human anti-human anti bodies (HAHA) at Visits 1, 21, 35, and 39

Timeframe: Visits 1 (Screening, Visit -2), 21 (Week 12), 35 (Month 6), and 39 (Month 18)

Number of participants who reported myelosuppression (anemia, leukopenia, neutropenia, and thrombocytopenia)

Timeframe: From first treatment (Visit 2) up to Visit 43 (Month 60)

Percent change from Screening (Visit 1) in complement (CH50) levels at Visit 9 (Week 4)

Timeframe: Visit 1 (Week -2) and Visit 9 (Week 4)

Number of participants classified as responders having CR who tested negative for Minimal Residual Disease (MRD)

Timeframe: From start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to course 6 or Week 32)

Ctrough and Cmax at the first infusion (Visit 2, Week 0) and sixth infusion (Visit 29, Week 20)

Timeframe: Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose)

AUC(0-inf) and AUC(0-672) after the first infusion (Visit 2, Week 0) and sixth infusion (Visit 29, Week 20)

Timeframe: Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose)

t1/2 after the first infusion (Visit 2, Week 0) and sixth infusion (Visit 29, Week 20)

Timeframe: Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose)

CL after the first infusion (Visit 2, Week 0) and sixth infusion (Visit 29, Week 20)

Timeframe: Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose)

Vss after the first infusion (Visit 2, Week 0) and sixth infusion (Visit 29, Week 20)

Timeframe: Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose)

Number of participants with progression or death

Timeframe: From time of randomization to first documented evidence of disease progression or death due to any cause, whichever came first, assessed over 2 years

Interventions:
  • Drug: Ofatumumab 500mg
  • Drug: Ofatumumab 1000mg
  • Drug: Fludarabine
  • Drug: Cyclophosphamide
    • Enrollment:
    61
    Primary completion date:
    2009-10-03
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Wierda WG, Kipps TJ, Durig J, Griskevicius L, Stilgenbauer S, Mayer J, et.al, Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia. Blood 2011 June 16; 117: 6450-6458
    Wierda WG, Kipps TJ, Dürig J, Griskevicius L, Stilgenbauer S, Mayer J et al.. Chemoimmunotherapy with Ofatumumab, Fludarabine and Cyclophosphamide (O-FC) in Previously Untreated Patients with Chronic Lymphocytic Leukemia (CLL). [Blood]. 2010;E pub ahead of print:
    Medical condition
    Leukaemia, Lymphocytic, Chronic
    Product
    ofatumumab
    Collaborators
    Not applicable
    Study date(s)
    January 2007 to May 2013
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • 1) Patients with active B-CLL and with an indication for treatment
    • 2) Age ≥ 18 years
    • 1) Any previous treatment for B-CLL or any other treatments that can be considered active against B-CLL
    • 2) Glucocorticoid unless given in doses ≤ 10 mg /day for other indications than B-CLL (e.g. asthma)
    Inclusion and exclusion criteria
    Inclusion criteria:
    • 1) Patients with active B-CLL and with an indication for treatment 2) Age ≥ 18 years 3) 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:
    • 1) Any previous treatment for B-CLL or any other treatments that can be considered active against B-CLL 2) Glucocorticoid unless given in doses ≤ 10 mg /day for other indications than B-CLL (e.g. asthma) 3) Known transformation of B-CLL 4) Known CNS involvement of B-CLL 5) Past or current malignancy, except for: a. Cervical carcinoma Stage 1B or less b. Non-invasive basal cell and squamous cell skin carcinoma c. Malignant melanoma with a complete response of a duration of > 10 years d. Other cancer diagnoses with a complete response of a duration of > 5 years 6) Chronic or current infectious disease requiring systemic treatment 7) Clinically significant cardiac disease 8) Significant concurrent, uncontrolled medical condition 9) History of significant cerebrovascular disease 10) Known HIV positive 11) Positive serology for hepatitis B, unless due to vaccination 12) Leukapheresis, except as a safety measure before chemotherapy 13) ECOG Performance Status of 3 or 4 14) Patients who at the time of inclusion are not expected to be able to complete the ofatumumab-FC regimen 15) Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 1 16) Current participation in any other interventional clinical study 17) Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder) 18) Breast feeding women or women with a positive pregnancy test at Visit 1 19) Women of childbearing potential not willing to use adequate contraception for up to one year after last dose of ofatumumab. Adequate contraception is defined as hormonal birth control or intrauterine device. For patients in the USA the use of a double barrier method is also considered adequate.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Plymouth, Devon, United Kingdom, PL68DH
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Houston, Texas, United States, 77030
    Status
    Study Complete
    Contact us

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    No longer a GSK study
    Actual primary completion date
    2009-10-03
    Actual study completion date
    2013-21-05

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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