Clinical trial NCT00410163: Ofatumumab With Fludarabine and Cyclophosphamide in B-CLL Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukaemia, Lymphocytic, Chronic
Keywords: B-cell
cyclophosphamide
fludarabine
Chronic Lymphocytic Leukemia
Ofatumumab
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-12-12
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate the safety and efficacy of two dose regimes of ofatumumab in combination with chemotherapy in previously untreated patients with B-CLL


Eligibility 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:

   1. Cervical carcinoma Stage 1B or less
   2. Non-invasive basal cell and squamous cell skin carcinoma
   3. Malignant melanoma with a complete response of a duration of \> 10 years
   4. 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.

Primary outcomes:
measure: 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)
measure: 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:
measure: Duration of Response
timeFrame: From time of initial response to disease progression or death, whichever came first, assessed over 2 years
measure: 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
measure: 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
measure: 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
measure: 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)
measure: 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)
measure: 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)
measure: Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia)
timeFrame: From first treatment (Visit 2) up to Visit 43 (Month 60)
measure: 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)
measure: 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)
measure: 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)
measure: 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)
measure: 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)
measure: 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)
measure: 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)
measure: 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
Other outcomes:
Locations:
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Plymouth
country: United Kingdom
facility: GSK Investigational Site
state: Devon
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Wierda WG, Kipps TJ, Durig J, Griskevicius L, Stilgenbauer S, Mayer J, Smolej L, Hess G, Griniute R, Hernandez-Ilizaliturri FJ, Padmanabhan S, Gorczyca M, Chang CN, Chan G, Gupta I, Nielsen TG, Russell CA; 407 Study Investigators. Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia. Blood. 2011 Jun 16;117(24):6450-8. doi: 10.1182/blood-2010-12-323980. Epub 2011 Apr 15.
citation: 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:
citation: Jewell RC, Kipps TJ, Durig J, Griskevicius L, Stilgenbauer S, Smolej L, Mayer J, Hess G, Hernandez-Ilizaliturri FJ, Padmanabhan-Iyer S, Fang L, Goldstein N, Gorczyca M, Gupta I, Lisby S, Wierda WG; Hx-CD20-407 Study Investigators. Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy. Leuk Lymphoma. 2017 Feb;58(2):348-356. doi: 10.1080/10428194.2016.1195497. Epub 2016 Jul 7.