Clinical trial NCT00349349: HuMax-CD20 in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Failing Fludarabine and Alemtuzumab
Official title: A Single-arm, International, Multi-center Trial of HuMax-CD20, a Fully Human Monoclonal Anti-CD20 Antibody, in Patients With B-cell Chronic Lymphocytic Leukemia Who Have Failed Fludarabine and Alemtuzumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukaemia, Lymphocytic, Chronic
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-07-07
Enrollment: 223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether HuMax-CD20 (ofatumumab) is effective in the treatment of patients failing both fludarabine and alemtuzumab.


Eligibility criteria: Inclusion Criteria:

1. Tumor cell phenotype consistent with B-CLL
2. Patients with active B-CLL and with an indication for treatment
3. Failing at least one fludarabine-containing treatment regimen
4. Failing at least one alemtuzumab-containing treatment regimen
5. ECOG Performance Status of 0, 1, or 2
6. Life expectancy of at least 4 months

Exclusion Criteria:

1. Previous treatment with alemtuzumab within 6 weeks prior to Visit 2
2. Previous autologous stem cell transplantation within 6 months prior to Visit 2
3. Allogeneic stem cell transplantation
4. Radioimmunotherapy

Primary outcomes:
measure: Number of Participants (Par.) Classified as Responders and Non-responders for Objective Response as Assessed by an Independent Endpoint Review Committee (IRC) in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines
timeFrame: Start of treatment (Week 0 of Visit 2) until Week 24
Secondary outcomes:
measure: Duration of Response
timeFrame: Start of treatment (Week 0 of Visit 2) until Week 24
measure: Progression-Free Survival (PFS)
timeFrame: Start of treatment (Week 0 of Visit 2) until Week 24
measure: Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment
timeFrame: Time from randomization (Week 0 of Visit 2) until the time of first administration of a CLL treatment other than ofatumumab (assessed for a median of 8.7 weeks currently [or up to 13.3 months])
measure: Overall Survival
timeFrame: Start of randomization (Week 0 of Visit 2) until death (up to a median of 17.1 weeks)
measure: Percent Change From Baseline to Week 7 in Peripheral CD5+CD19+ Cell Counts
timeFrame: Baseline (Visit 2) until Week 7 (Visit 9)
measure: Percent Change From Baseline to Week 7 in Peripheral CD5+CD20+ Cell Counts
timeFrame: Baseline (Visit 2) until Week 7 (Visit 9)
measure: Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) to Week 24 (Visit 14)
timeFrame: Baseline (Visit 2) until Week 24 (Visit 14)
measure: Number of Participants With Complete Resolution of Constitutional Symptoms at Week 24
timeFrame: Baseline (Visit 2) and Week 24
measure: Number of Participants With Complete Resolution of Lymphadenopathy
timeFrame: Baseline (Visit 2) to end of study (up to Week 24)
measure: Number of Participants With Improvement on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale at Week 24
timeFrame: Baseline (Visit 2) and Week 24
measure: Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening
timeFrame: Screening (Visit 1, <=14 days prior to Visit 2)
measure: Number of Participants With Improvement in Hemoglobin
timeFrame: Baseline (Visit 2) to Week 28
measure: Number of Participants With Improvement in Thrombocytopenia (Thromb.)
timeFrame: Baseline (Visit 2) to Week 28
measure: Number of Participants With Complete Resolution of Hepatomegaly
timeFrame: Baseline (Visit 2) until Week 24
measure: Number of Participants With Improvement in Neutropenia
timeFrame: Baseline (Visit 2) to Week 28
measure: Number of Participants With Complete Resolution of Splenomegaly
timeFrame: Baseline (Visit 2) until Week 24
measure: Number of Participants Who Experienced Any Adverse Event
timeFrame: From first infusion (Visit 2/Week 0) to Visit 21 (Month 24 of follow-up [up to Month 48]) or time of withdrawal (treatment and follow-up)
measure: Cmax and Ctrough at Dose 1 (Visit 2, Week 0), Dose 8 (Visit 9, Week 7), and Dose 12 (Visit 14, Week 24)
timeFrame: Visit 2 (Week 0), Visit 9 (Week 7), and Visit 14 (Week 24)
measure: AUC (0-inf) and AUC(0-tau) at Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)
timeFrame: Visit 9 (Week 7) and Visit 14 (Week 24)
measure: Half-life (t1/2) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)
timeFrame: Visit 9 (Week 7) and Visit14 (Week 24)
measure: Clearance (CL) After Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)
timeFrame: Visit 9 (Week 7) and Visit 14 (Week 24)
measure: Volume of Distribution at Steady State (Vss) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)
timeFrame: Visit 9 (Week 7) and Visit 14 (Week 24)
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Wierda WG, Padmanabhan S, Chan GW, Gupta IV, Lisby S, Osterborg A; Hx-CD20-406 Study Investigators. Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study. Blood. 2011 Nov 10;118(19):5126-9. doi: 10.1182/blood-2011-04-348656. Epub 2011 Aug 19.
citation: Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, Robak T, Furman RR, Hillmen P, Trneny M, Dyer MJ, Padmanabhan S, Piotrowska M, Kozak T, Chan G, Davis R, Losic N, Wilms J, Russell CA, Osterborg A; Hx-CD20-406 Study Investigators. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010 Apr 1;28(10):1749-55. doi: 10.1200/JCO.2009.25.3187. Epub 2010 Mar 1.
citation: Struemper H, Sale M, Patel BR, Ostergaard M, Osterborg A, Wierda WG, Hagenbeek A, Coiffier B, Jewell RC. Population pharmacokinetics of ofatumumab in patients with chronic lymphocytic leukemia, follicular lymphoma, and rheumatoid arthritis. J Clin Pharmacol. 2014 Jul;54(7):818-27. doi: 10.1002/jcph.268. Epub 2014 Jan 28.