Ofatumumab Maintenance Treatment vs No Further Treatment in Relapsed CLL Responding to Induction TherapyPROLONG
Trial overview
Progression-free survival, as assessed by the Independent Review Committee (IRC)
Timeframe: From randomization until progression or death (up to 84 months)
Progression-free survival, as assessed by the Investigator
Timeframe: From randomization until progression or death (up to 84 months)
Number of participants with Grade 3 and above adverse event of infection
Timeframe: 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)
Change from Baseline in cluster of differentiation (CD) CD5+CD19+ and CD5-CD19+ cell counts at the indicated time points
Timeframe: Baseline and every two months from Month 3 until Month 25 and at every follow-up visit (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)
Timeframe: From randomization until the end of the study (up to 84 months)
Overall survival
Timeframe: From randomization until death (up to 84 months)
Time to next therapy
Timeframe: From randomization until the end of the study (up to 84 months)
Number of participants with positive and negative human anti-human Antibody (HAHA) at the indicated time points
Timeframe: 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)
Progression-free survival after next-line therapy
Timeframe: From randomization until progression or death (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
Timeframe: From Baseline until the end of the study (up to 84 months)
Total plasma clearance (CL) of ofatumumab
Timeframe: 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
Timeframe: 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
Timeframe: 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)
Mean change from Baseline in the immunoglobulin (Ig) antibodies IgA, IgG, and IgM at indicated time points
Timeframe: Baseline, every six months during treatment, and after last treatment visit and/or upon relapse (up to 24 months)
Cmax and Ctrough of ofatumumab
Timeframe: 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)
Time to progression after next-line therapy
Timeframe: From randomization until progression or death (up to 84 months)
Number of participants diagnosed with autoimmune hemolytic anemia (AIHA)
Timeframe: From randomization until the end of the study (up to 24 months)
Number of participants with any adverse event (AE) or serious adverse event (SAE)
Timeframe: 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 who received at least one transfusion during the study
Timeframe: From randomization until the end of the study (up to 24 months)
AUC(0-tau) of ofatumumab
Timeframe: 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)
Number of participants who were positive and negative for minimal residual disease (MRD) at any visit
Timeframe: From randomization until the end of the study (up to 84 months)
Number of participants with improvement in response from Baseline
Timeframe: From Baseline until the end of the study (up to 24 months)
Change from Baseline in the Quality of Life Status as assessed by the EuroQol-5D (EQ-5D) Scale
Timeframe: 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
Timeframe: From randomization until the end of the study (up to 84 months)
Number of participants with a Grade 3 or Grade 4 myelosuppression (anemia, neutropenia, or thrombocytopenia) at indicated time points
Timeframe: 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 with the indicated constitutional or B-symptoms at the indicated time points
Timeframe: From Screening 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
Timeframe: From randomization until the end of the study (up to 84 months)
Participation 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
- 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
- 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
- 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).
Trial location(s)
No location data available.
Study documents
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
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.