Overview

This trial is active, not recruiting.

Condition leukaemia, lymphocytic, chronic
Treatments ofatumumab, physicians' choice
Phase phase 3
Sponsor GlaxoSmithKline
Start date April 2011
End date March 2014
Trial size 122 participants
Trial identifier NCT01313689, 114242

Summary

The purpose of this study is to confirm the clinical benefit observed in the pivotal registration study, Hx-CD20-406. The Committee for Medicinal Products for Human Use (CHMP) required that a randomized study be conducted in CLL patients with bulky fludarabine-refractory disease as a specific obligation for grant of conditional approval for ARZERRA™ in the European Union (EU). This study will compare ofatumumab with the physicians' choice of therapy.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model factorial assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Biological
ofatumumab
Ofatumumab IV, initial dose 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks. After 24 weeks of ofatumumab treatment, patients who have achieved at least stable disease or better, and whom the investigator would deem appropriate for the therapy to continue, would undergo a second randomisation (2:1) to either 1) an additional ofatumumab dose regimen of 2000 mg once every 4 weeks for up to an additional 24 weeks, or 2) no further therapy (i.e. observation only).
(Active Comparator)
Physicians' choice of treatment
physicians' choice
Non-ofatumumab containing regimen as per physicians' choice for up to 6 months. Permitted therapies include treatments approved for CLL, and well established standards of care for CLL.

Primary Outcomes

Measure
Progression-free Survival (PFS) as assessed by Independent Review Committee (IRC)
time frame: From the randomization date up to 60 months post the randomization date.

Secondary Outcomes

Measure
Progression-free Survival (PFS) as assessed by Investigator
time frame: From the randomization date up to 60 months post the randomization date.
Overall response rate (ORR) as assessed by the IRC
time frame: From the randomization date up to 60 months post the randomization date.
Overall response rate (ORR) as assessed by the Investigator
time frame: From the randomization date up to 60 months post the randomization date.
Overall Survival
time frame: From the randomization date up to 60 months post the randomization date.
Time to progression as assessed by IRC
time frame: From the randomization date up to 60 months post the randomization date.
Time to next anti-cancer therapy by Investigator
time frame: From the randomization date up to 60 months post the randomization date.
Time to response as assessed by the IRC
time frame: From the randomization date up to 60 months post the randomization date.
Duration of response as assessed by the IRC
time frame: From the randomization date up to 60 months post the randomization date.
Number of participants with any adverse event (AE), any serious adverse event (SAE), any fatal serious adverse event (FSAE), or deaths
time frame: From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy (Median follow-up approximately 28.9 months)
Number of participants with any adverse event (AE) of special interest
time frame: From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy (Median follow-up approximately 28.9 months)
Mean Immunoglobulin (Ig) antibodies IgA, IgG, and IgM over time
time frame: Screening and every 3 months during treatment, every 6 months after last treatment until PD or until 30 Month Follow-up Visit
Number of participants who were positive or negative for Human Anti-Human Antibodies (HAHA) post-OFA therapy
time frame: From the randomization date up to 60 months post the randomization date.
Changes from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 item module (EORTC QLQ-CLL 16)
time frame: From the randomization date up to 60 months post the randomization date.
Mean Health Change Questionnaire (HCQ) score
time frame: From the randomization date up to 60 months post the randomization date.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adults with documented diagnosis of active CLL requiring treatment - Bulky lymphadenopathy, defined as at least 1 lymph node >5 cm - Must be refractory to fludarabine treatment - Age 18 yrs or older - At least 2 prior therapies for CLL - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 - Signed written informed consent Exclusion Criteria: - Prior allogeneic stem cell transplant at any time, or autologous stem cell transplant within 6 months - Treatment with any unapproved drug substance or experimental therapy within 4 weeks, or currently participating in another interventional clinical study - CLL transformation, prolymphocytic leukemia, or central nervous system (CNS) involvement of CLL - Active autoimmune hemolytic anemia (AIHA) requiring treatment except if associated with progressive disease requiring anti-CLL treatment - Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment - Human immunodeficiency virus (HIV) positive - Significant concurrent, uncontrolled medical condition - Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry - Non-protocol corticosteroid usage except a maintenance dose corresponding to less than or equal to 10 mg prednisone - Abnormal lab values: Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance), or total bilirubin > 2.0 times upper normal limit (unless due to liver involvement of CLL or due to Gilbert's syndrome), or alanine transaminase (ALT) > 2.5 times upper normal limit (unless due to liver involvement of CLL) - Known or suspected hypersensitivity to ofatumumab - Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception

Additional Information

Official title An Open Label, Multicenter Study Investigating the Safety and Efficacy of Ofatumumab Therapy Versus Physicians' Choice in Patients With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukaemia (CLL)
Description Patients with CLL that is refractory to fludarabine have few treatment options and a poor prognosis. There is a continued need for new therapies for these CLL patients, as demonstrated by the limited responses and substantial toxicities with existing therapies. This is supported by the lack of a consensus around standard of care treatment for CLL patients with bulky fludarabine-refractory disease. The objective of this study is to confirm the response rate and disease control in the refractory setting through a controlled trial comparing ofatumumab with the physicians' choice of therapy in fludarabine-refractory, bulky lymphadenopathy patients. After 24 weeks of treatment with ofatumumab, patients will be further randomized to either extended ofatumumab treatment or observation. Patients on the physicians' choice arm will have the option of receiving ofatumumab if they experience progressive disease.
Trial information was received from ClinicalTrials.gov and was last updated in October 2014.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.