Overview

This trial is active, not recruiting.

Condition leukaemia, lymphocytic, chronic
Treatments ofatumumab, observation
Phase phase 3
Sponsor GlaxoSmithKline
Start date May 2010
End date June 2014
Trial size 480 participants
Trial identifier NCT01039376, 112517

Summary

The purpose of this study is to determine if maintenance therapy with ofatumumab will prolong remission in patients with CLL who have responded to second or third line treatment. This study will also evaluate the safety of ofatumumab maintenance compared to observation (the current standard of care). This study was co-developed with the HOVON and NORDIC CLL group and will be conducted as a collaborative effort with GSK.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Ofatumumab Treatment: 300 mg IV Week 1 followed by 1000 mg IV Week 2 1000 mg IV (a dose every 8 weeks for up to 2 years following the first 1000 mg dose)
ofatumumab
Ofatumumab for maintenance therapy as IV infusions every 8 weeks . The first dose will be 300 mg followed 1 week later by 1000 mg and 1000 mg every 8 weeks thereafter for up to 2 years).
(Other)
Disease status assessments to determine subject response or progression will be performed approximately every 8 weeks for up to 2 years for both arms according to IWCLL criteria
observation
Observation/Safety Evaluation

Primary Outcomes

Measure
Progression-free Survival, as Assessed by the Investigator
time frame: From randomization until progression or death (up to 84 months)
Progression-free Survival, as Assessed by the Independent Review Committee (IRC)
time frame: From randomization until progression or death (up to 84 months)

Secondary Outcomes

Measure
Overall Survival
time frame: From randomization until death (up to 84 months)
Number of Participants With Improvement in Response From Baseline
time frame: From Baseline until the end of the study (up to 24 months)
Time to Next Therapy
time frame: From randomization until the end of the study (up to 84 months)
Progression-free Survival After Next-line Therapy
time frame: From randomization until progression or death (up to 84 months)
Time to Progression After Next-line Therapy
time frame: From randomization until progression or death (up to 84 months)
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16)
time frame: From randomization until the end of the study (up to 84 months)
Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score
time frame: From randomization until the end of the study (up to 84 months)
Change From Baseline in the Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale
time frame: From randomization until the end of the study (up to 84 months)
Number of Participants With an Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status at the Indicated Time Points
time frame: From randomization until the end of the study (up to 84 months)
Number of Participants With the Indicated Constitutional or B-symptoms at the Indicated Time Points
time frame: From Screening until the end of the study (up to 84 months)
Number of Participants With Grade 3 and Above Adverse Event of Infection
time frame: From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 (up to 84 months)
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
time frame: From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 (up to 24 months for non-serious AEs and 84 months for SAEs)
Number of Participants With a Grade 3 or Grade 4 Myelosuppression (Anemia, Neutropenia, or Thrombocytopenia) at Indicated Time Points
time frame: From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 (up to 24 months)
Number of Participants Who Received at Least One Transfusion During the Study
time frame: From randomization until the end of the study (up to 24 months)
Number of Participants Diagnosed With Autoimmune Hemolytic Anemia (AIHA)
time frame: From randomization until the end of the study (up to 24 months)
Number of Participants With Positive and Negative Human Anti-human Antibody (HAHA) at the Indicated Time Points
time frame: Pre-dose (Visit 1), Months 7, 13, 19, and 25 during treatment and at 3 and 6 months after last ofatumumab dose (up to 30 months)
Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM at Indicated Time Points
time frame: Baseline, every six months during treatment, and after last treatment visit and/or upon relapse (up to 24 months)
Number of Participants Who Were Positive and Negative for Minimal Residual Disease (MRD) at Any Visit
time frame: From randomization until the end of the study (up to 84 months)
Change From Baseline in Cluster of Differentiation (CD) CD5+CD19+ and CD5-CD19+ Cell Counts at the Indicated Time Points
time frame: Baseline and every two months from Month 3 until Month 25 and at every follow-up visit (up to 84 months)
Summary of Covariates to Compute Cox Proportional Hazards Regression Model for Relationship Between Investigator Assessed Progression-free Survival and the Indicated Prognostic Markers
time frame: From Baseline until the end of the study (up to 84 months)
Cmax and Ctrough of Ofatumumab
time frame: Pre-dose, Day 1, Day 8, Months 3, 5, 7, 9, 13, 19 and 25; and at 3 and 6 months post last dose (up to 30 months)
Total Plasma Clearance (CL) of Ofatumumab
time frame: Pre-dose, Day 1, Day 8, Months 3, 5, 7, 9, 13, 19 and 25; and at 3 and 6 months post last dose (up to 30 months)
AUC(0-tau) of Ofatumumab
time frame: Pre-dose, Day 1, Day 8, Months 3, 5, 7, 9, 13, 19 and 25; and at 3 and 6 months post last dose (up to 30 months)
Vss of Ofatumumab
time frame: Pre-dose, Day 1, Day 8, Months 3, 5, 7, 9, 13, 19 and 25; and at 3 and 6 months post last dose (up to 30 months)
Plasma Half-life (t1/2) of Ofatumumab
time frame: Pre-dose, Day 1, Day 8, Months 3, 5, 7, 9, 13, 19 and 25; and at 3 and 6 months post last dose (up to 30 months)

Eligibility Criteria

Male or female participants of any age.

Inclusion Criteria: - Adults with documented diagnosis of CLL based on the modified IWCLL updated NCI-WG guidelines (Hallek, 2008) - At least PR according to the revised 2008 NCI-WG CLL criteria, within 3 months of the response assessment after the last dose of 2nd/3rd line treatment - The anti-leukemic treatment before study entry should have been at least 3 months or 3 cycles - ECOG Performance Status of 0-2 - Signed written informed consent prior to performing any study-specific procedures Exclusion Criteria: - Known primary or secondary fludarabine-refractory subjects, defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months - Prior maintenance therapy - Known transformation of CLL (eg.Richter's transformation), prolymphocytic leukemia (PLL), or CNS involvement of CLL - Active Autoimmune hemolytic anemia (AIHA) requiring treatment except if in the opinion of the investigator and medical monitor it is thought not to affect the subject's safety, the conduct of the study or the interpretation of the data - Previous autologous or allogeneic stem cell transplantation - Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis B or C - Other past or current malignancy (with the exception of basal cell carcinoma or the skin or in situ carcinoma of the cervix or breasts) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry except if in the opinion of the investigator and medical monitor it is thought not to affect the subject's safety, the conduct of the study or the interpretation of the data - Clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months prior to screening, congestive heart failure, and arrhythmia requiring therapy, with the exception of exta systoles or minor conduction abnormalities except if in the opinion of the investigator and medical monitor it is thought not to affect the subject's safety, the conduct of the study or the interpretation of the data - History of significant cerebrovascular disease or event with symptoms or sequelae - Significant concurrent, uncontrolled medical condition that in the opinion of the investigator or GSK medical monitor contraindicates participation in this study - Other anti-leukemic use of medications including glucocorticoids - Known HIV positive - Screening laboratory values: platelets <50 x 109/L, neutrophils<1.0 x 109/L, Creatinine > 1.5 X upper normal limit (unless normal creatinine clearance), total bilirubin >1.5 X upper normal limit, ALT >2.5 X upper normal limit (unless due to liver involvement of CLL), alkaline phosphase > 2.5 X upper normal limit - Known or suspected hypersensitivity to ofatumumab that in the opinion of the investigator or medical monitor contraindicates study participation - Subjects who have received treatment with any non-marketed drug substance or experimental therapy within 5-terminal half-lives or 4 weeks whichever is longer prior to first dose of study medication or currently participating in any other interventional clinical study Note: Participation in any other interventional clinical study after disease progression during post PD follow-up is permitted - Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last ofatumumab dose. Adequate contraception is defined as abstinence, oral hormonal birth control, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device, and male partner sterilization if male partner is sole partner for that subject. For females in the USA, the use of a double barrier method is also considered adequate (condom or occlusive cap plus spermicidal agent).

Additional Information

Official title A Phase III, Open Label, Randomized, Multicenter Trial of Ofatumumab Maintenance Treatment Versus no Further Treatment in Subjects With Relapsed Chronic Lymphocytic Leukemia (CLL) Who Have Responded to Induction Therapy
Trial information was received from ClinicalTrials.gov and was last updated in April 2015.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.