Last updated: 11/03/2018 13:02:38
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.

Ofatumumab Maintenance Treatment vs No Further Treatment in Relapsed CLL Responding to Induction TherapyPROLONG

GSK study ID
112517
See study documents
Clinicaltrials.gov ID
NCT01039376
EudraCT ID
2009-012518-39
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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 description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:

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)

Secondary outcomes:

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)

Interventions:
  • Other: Observation
  • Vaccine: Ofatumumab
    • Enrollment:
    480
    Primary completion date:
    2014-19-06
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Leukaemia, Lymphocytic, Chronic
    Product
    ofatumumab
    Collaborators
    Not applicable
    Study date(s)
    May 2010 to July 2021
    Type
    Interventional
    Phase
    2/3

    Participation criteria

    Sex
    Female & Male
    Age
    Not applicable
    Accepts healthy volunteers
    none
    • 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
    Inclusion and exclusion criteria
    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).

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Refer to study documents

    Recruitment status
    No longer a GSK study
    Actual primary completion date
    2014-19-06
    Actual study completion date
    Not applicable

    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.

    Additional information about the trial

    Additional information
    Not applicable
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