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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01039376




Registration number
NCT01039376
Ethics application status
Date submitted
23/12/2009
Date registered
25/12/2009

Titles & IDs
Public title
Ofatumumab Maintenance Treatment vs No Further Treatment in Relapsed CLL Responding to Induction Therapy
Scientific 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
Secondary ID [1] 0 0
COMB157C2301
Secondary ID [2] 0 0
112517
Universal Trial Number (UTN)
Trial acronym
PROLONG
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukaemia, Lymphocytic, Chronic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Ofatumumab
Other interventions - Observation

Experimental: ARM A: Ofatumumab - 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)

Other: ARM B: Observation and assessments as per Arm A - Disease status assessments to determine subject response or progression performed approximately every 8 weeks for up to 2 years for both arms according to IWCLL criteria


Treatment: Other: Ofatumumab
Ofatumumab for maintenance therapy as IV infusions every 8 weeks . The first dose was 300 mg followed 1 week later by 1000 mg and 1000 mg every 8 weeks thereafter for up to 2 years.

Other interventions: Observation
Observation/Safety Evaluation

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival, as Assessed by the Investigator
Timepoint [1] 0 0
From randomization until progression or death (up to 79 months)
Primary outcome [2] 0 0
Progression-free Survival, as Assessed by the Independent Review Committee (IRC)
Timepoint [2] 0 0
From randomization until progression or death (up to 79 months)
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
From randomization until death (up to 88 months)
Secondary outcome [2] 0 0
Number of Participants With Improvement in Response From Baseline
Timepoint [2] 0 0
From Baseline until the end of the study (up to 88 months)
Secondary outcome [3] 0 0
Time to Next Therapy
Timepoint [3] 0 0
From randomization until the end of the study (up to 88 months)
Secondary outcome [4] 0 0
Progression-free Survival After Next-line Therapy
Timepoint [4] 0 0
From randomization until progression or death (up to 88 months)
Secondary outcome [5] 0 0
Time to Progression After Next-line Therapy
Timepoint [5] 0 0
From randomization until progression or death (up to 88 months)
Secondary outcome [6] 0 0
Change From Baseline (BL) in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16)
Timepoint [6] 0 0
From randomization until the end of the study (up to 47 months)
Secondary outcome [7] 0 0
Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score
Timepoint [7] 0 0
From randomization until the end of the study (up to 47 months)
Secondary outcome [8] 0 0
Change From Baseline in the Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale
Timepoint [8] 0 0
From screening until the end of the study (up to 47 months)
Secondary outcome [9] 0 0
Number of Participants With an Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status at the Indicated Time Points
Timepoint [9] 0 0
From randomization until the end of the study (up to 88 months)
Secondary outcome [10] 0 0
Number of Participants With the Indicated Constitutional or B-symptoms at the Indicated Time Points
Timepoint [10] 0 0
From Screening until the end of the study (up to 88 months)
Secondary outcome [11] 0 0
Number of Participants With Grade 3 and Above Adverse Event of Infection
Timepoint [11] 0 0
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 26 months)
Secondary outcome [12] 0 0
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Timepoint [12] 0 0
From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until end of study for SAEs (88 months)
Secondary outcome [13] 0 0
Number of Participants With a Grade 3 or Grade 4 Myelosuppression (Anemia, Neutropenia, or Thrombocytopenia) at Indicated Time Points
Timepoint [13] 0 0
From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until the end of the study for SAEs (88 months)
Secondary outcome [14] 0 0
Number of Participants Who Received at Least One Transfusion During the Study
Timepoint [14] 0 0
From randomization until the end of the study (up to 88 months)
Secondary outcome [15] 0 0
Number of Participants Diagnosed With Autoimmune Hemolytic Anemia (AIHA)
Timepoint [15] 0 0
From randomization until the end of the study (up to 88 months)
Secondary outcome [16] 0 0
Number of Participants With a Positive Anti-ofatumumab Antibody (Human Anti-human Antibody; HAHA) Result
Timepoint [16] 0 0
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)
Secondary outcome [17] 0 0
Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM at Indicated Time Points
Timepoint [17] 0 0
Baseline, every six months during treatment, and after last treatment visit and/or upon relapse (up to 88 months)
Secondary outcome [18] 0 0
Number of Participants Who Were Positive and Negative for Minimal Residual Disease (MRD) at Any Visit
Timepoint [18] 0 0
From randomization until the end of the study (up to 88 months)
Secondary outcome [19] 0 0
Change From Baseline in Cluster of Differentiation (CD) CD5+CD19+ and CD5-CD19+ Cell Counts at the Indicated Time Points
Timepoint [19] 0 0
Baseline and every two months from Month 3 until Month 25 and at every followup (up to 88 months)
Secondary outcome [20] 0 0
Summary of Covariates to Compute Cox Proportional Hazards Regression Model for Relationship Between Investigator Assessed Progression-free Survival and the Indicated Prognostic Markers
Timepoint [20] 0 0
From Baseline until the end of the study (up to 79 months)
Secondary outcome [21] 0 0
Cmax and Ctrough of Ofatumumab
Timepoint [21] 0 0
Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)
Secondary outcome [22] 0 0
Total Plasma Clearance (CL) of Ofatumumab
Timepoint [22] 0 0
Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)
Secondary outcome [23] 0 0
AUC(0-tau) of Ofatumumab
Timepoint [23] 0 0
Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)
Secondary outcome [24] 0 0
Vss of Ofatumumab
Timepoint [24] 0 0
Day 1 Month 1 ( Cycle 1) through Month 7 ( Cycle 4)
Secondary outcome [25] 0 0
Plasma Half-life (t1/2) of Ofatumumab
Timepoint [25] 0 0
Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)

Eligibility
Key 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
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 10x9/L, neutrophils<1.0 x 10x9/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
* 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Darlinghurst
Recruitment hospital [2] 0 0
Novartis Investigative Site - Randwick
Recruitment hospital [3] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [4] 0 0
Novartis Investigative Site - East Melbourne
Recruitment hospital [5] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Idaho
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Louisiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
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United States of America
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Missouri
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United States of America
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Nevada
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United States of America
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New Jersey
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New Mexico
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New York
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North Carolina
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United States of America
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Pennsylvania
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United States of America
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South Carolina
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United States of America
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Tennessee
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United States of America
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Utah
Country [25] 0 0
Argentina
State/province [25] 0 0
Buenos Aires
Country [26] 0 0
Argentina
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Santa Fe
Country [27] 0 0
Argentina
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Ciudad Autonoma de Buenos Aires
Country [28] 0 0
Belgium
State/province [28] 0 0
Antwerpen
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Belgium
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Brugge
Country [30] 0 0
Belgium
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Brussels
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Belgium
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Gent
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Belgium
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Hasselt
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Belgium
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Roeselare
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Belgium
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Wilrijk
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Brazil
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Bahía
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Brazil
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Goiás
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Brazil
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Rio Grande Do Sul
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Brazil
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São Paulo
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Alberta
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Ontario
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Brno
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Hradec Kralove
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Olomouc
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Czechia
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Pelhrimov
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Czechia
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Praha 10
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Herlev
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Roskilde
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Finland
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Helsinki
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Finland
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Jyvaskyla
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Finland
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Pori
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Finland
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Tampere
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Finland
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Turku
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France
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Blois cedex
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France
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Caen cedex 5
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France
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Clermont-Ferrand Cedex 1
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France
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Dijon
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France
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Lille cedex
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France
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Marseille Cedex 9
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France
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Mulhouse
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France
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Pessac cedex
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France
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Saint Pierre cedex
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France
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Strasbourg cedex
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France
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Toulouse cedex 9
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France
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Vandoeuvre-Les-Nancy
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Greece
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Athens,
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Greece
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Athens
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Greece
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Piraeus
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Greece
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Thessaloniki
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Kecskemet
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Hungary
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Szeged
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India
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Ahmedabad
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India
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Mumbai
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India
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Pune
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Israel
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Afula
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Kfar Saba
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Israel
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Nahariya
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Israel
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Petach-Tikva
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Israel
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Ramat Gan
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Israel
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Rehovot
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Israel
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Tel-Aviv
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Israel
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Zrifin
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Italy
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Emilia-Romagna
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Italy
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Lazio
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Italy
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Piemonte
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Italy
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Toscana
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Korea, Republic of
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Seoul
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Netherlands
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Amersfoort
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Netherlands
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Amsterdam
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Blaricum
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Netherlands
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Breda
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Netherlands
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Den Bosch
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Den Haag
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Deventer
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Netherlands
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Dordrecht
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Netherlands
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Enschede
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Netherlands
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Groningen
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Hoofddorp
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Leiden
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Maastricht
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Rotterdam
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Netherlands
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Sittard-geleen
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Netherlands
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Tilburg
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Norway
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Oslo
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Poland
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Bialystok
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Poland
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Chorzow
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Poland
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Slupsk
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Poland
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Szczecin
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Poland
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Warszawa
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Poland
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Wroclaw
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Puerto Rico
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San Juan
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Russian Federation
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Kazan
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Russian Federation
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Moscow
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Russian Federation
State/province [120] 0 0
Novosibirsk
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Russian Federation
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Penza
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Russian Federation
State/province [122] 0 0
St'Petersburg
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Russian Federation
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St. Petersburg
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Russian Federation
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Volgograd
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Spain
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Hospitalet de Llobregat (Barcelona)
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Spain
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Madrid
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Spain
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Salamanca
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Spain
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Sevilla
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Spain
State/province [129] 0 0
Toledo
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Spain
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Zaragoza
Country [131] 0 0
Sweden
State/province [131] 0 0
Goteborg
Country [132] 0 0
Sweden
State/province [132] 0 0
Linkoping
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Sweden
State/province [133] 0 0
Lulea
Country [134] 0 0
Sweden
State/province [134] 0 0
Orebro
Country [135] 0 0
Sweden
State/province [135] 0 0
Stockholm
Country [136] 0 0
Sweden
State/province [136] 0 0
Uppsala
Country [137] 0 0
Turkey
State/province [137] 0 0
Ankara
Country [138] 0 0
Turkey
State/province [138] 0 0
Istanbul
Country [139] 0 0
Turkey
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Izmir
Country [140] 0 0
Ukraine
State/province [140] 0 0
Cherkasy
Country [141] 0 0
Ukraine
State/province [141] 0 0
Dnipropetrovsk
Country [142] 0 0
Ukraine
State/province [142] 0 0
Kharkiv
Country [143] 0 0
Ukraine
State/province [143] 0 0
Khmelnytskyi
Country [144] 0 0
Ukraine
State/province [144] 0 0
Kyiv
Country [145] 0 0
Ukraine
State/province [145] 0 0
Lviv
Country [146] 0 0
Ukraine
State/province [146] 0 0
Makiivka
Country [147] 0 0
Ukraine
State/province [147] 0 0
Vinnitsa
Country [148] 0 0
Ukraine
State/province [148] 0 0
Zhytomyr

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.