Clinical trial NCT00802737: Efficacy and Safety of Ofatumumab Retreatment and Maintenance Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL)
Official title: A Single-arm, International, Multi-center Trial Investigating the Efficacy and Safety of Ofatumumab Retreatment and Maintenance in CLL Patients Who Progressed Following Response or Stable Disease After Ofatumumab Treatment in Hx-CD20-406
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Leukaemia, Lymphocytic, Chronic
Keywords: Maintenance
Retreatment
Chronic lymphocytic leukemia
B-Cell Chronic Lymphocytic Leukemia
Ofatumumab
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Genmab
First posted: 2008-12-05
Enrollment: 29
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: The purpose of the trial is to investigate the efficacy and safety of ofatumumab retreatment and maintenance in patients with chronic lymphocytic leukemia who have previously responded or had disease stabilization after ofatumumab in an ongoing trial (Hx-CD20-406).


Eligibility criteria: Inclusion Criteria:

* Has responded to ofatumumab treatment (CR, nPR, PR) or has had SD at least up to and including visit number 14 (24 weeks after first infusion) in the Hx-CD20-406 trial.
* Has disease progression after visit number 14 (24 weeks after first infusion) in the Hx CD20 406 trial.
* Received at least eight ofatumumab infusions.
* Has active CLL with an indication for treatment.
* Has Eastern Cooperative Oncology Group (ECOG) performance status grade 0, 1 or 2.
* Provides signed informed consent, following receipt of verbal and written information about the trial, before any trial related activity is carried out.
* If previously treated in GEN416 (this trial), the patient must have achieved CR with subsequent disease progression 24 weeks or later after the first infusion in the GEN416 trial.

Exclusion Criteria:

* The disease has transformed to more aggressive B-cell malignancies (e.g. diffuse large B-cell lymphoma, Richter's syndrome or prolymphocytic leukemia).
* Has a suspected treatment requiring malignancy other than CLL.
* Has received treatment other than ofatumumab within two weeks prior to visit 2.
* Has clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from visit 1, congestive heart failure (NYHA III IV), and arrhythmia requiring therapy, with the exception of clinically non-significant extra systoles or minor conduction abnormalities.
* Has significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.
* Has a history of significant cerebrovascular disease.
* Is known HIV positive.
* Has positive serology for hepatitis B, defined as a positive test for HBsAg and/or positive tests for both anti-HBs and anti-HBc.
* Has known or suspected hypersensitivity to components of the IMP.
* Has received treatment with any non-marketed drug substance or experimental therapy other than ofatumumab within four weeks prior to visit 2.
* Currently participates in any other interventional clinical trial other than Hx-CD20-406.
* Known or suspected to not being able to comply with a trial protocol (e.g. due to alcoholism, drug dependency or psychiatric disorder).
* Is breast feeding (women only).
* Has a positive pregnancy test at screening (women only).
* Is not willing to use adequate contraception during the trial and one year after last dose of ofatumumab (women only). Adequate contraception is defined as hormonal birth control or intrauterine device. For patients in the US the use of double barrier method is considered adequate.

Primary outcomes:
measure: Number of Participants (Par.) Classified as Responders (Rs) and Non-responders (NRs) for Objective Response in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines
timeFrame: Start of treatment (Week 0/Visit 2) until Week 52
Secondary outcomes:
measure: Duration of Response
timeFrame: From the time of the initial response until progression or death (average of 14.1 study months)
measure: Progression-Free Survival (PFS)
timeFrame: Start of treatment (Week 0 of Visit 2) until progression or death (average of 14.1 study months)
measure: Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment
timeFrame: Time from start of study treatment (Week 0 of Visit 2) until the time of first administration of a CLL treatment other than ofatumumab (average of 14.8 study months)
measure: Overall Survival (OS)
timeFrame: Time from start of study treatment (Week 0 of Visit 2) until date of death or time that participant was no longer followed (median of 18.0 months)
measure: Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 4
timeFrame: Baseline (Visit 2) and Month 4
measure: Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 12
timeFrame: Baseline (Visit 2) and Month 12
measure: Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 24
timeFrame: Baseline (Visit 2) and Month 24
measure: Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab
timeFrame: Screening and post ofatumumab (up to Study Month 32)
measure: Number of Participants Who Experienced Any Adverse Event
timeFrame: From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])
measure: Number of Participants With the Indicated Major Infections
timeFrame: From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])
measure: Number of Participants With Infections Requiring Hospitalization or Intravenous Antibiotics
timeFrame: From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])
measure: Cmax and Ctrough at Visit 2 (Week 0) and at Visit 14 (Month 4)
timeFrame: Visit 2 (Week 0) and Visit 14 (Month 4)
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Örebro
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: van Oers MH, Kuliczkowski K, Smolej L, Petrini M, Offner F, Grosicki S, Levin MD, Gupta I, Phillips J, Williams V, Manson S, Lisby S, Geisler C; PROLONG study investigators. Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open-label, multicentre, randomised phase 3 study. Lancet Oncol. 2015 Oct;16(13):1370-9. doi: 10.1016/S1470-2045(15)00143-6. Epub 2015 Sep 13.