Leukaemia, Lymphocytic, Chronic Clinical Trial
Official title:
A Phase II, Multi-centre Study Investigating the Safety and Efficacy of Ofatumumab and Bendamustine Combination in Patients With Untreated or Relapsed Chronic Lymphocytic Leukaemia (CLL)
This is a Phase II, open label, single arm, multi-centre study investigating the safety and
efficacy of ofatumumab plus bendamustine in subjects with untreated or relapsed CLL.
Each subject from the screening phase who is willing to participate in the study and is
found eligible according to the inclusion and exclusion criteria will enter the treatment
phase and will receive a maximum of 6 Cycles of study treatment (ofatumumab plus
bendamustine). All subjects will receive 3 Cycles of study treatment (Cycles 1, 2 and 3).
Eligibility to receive study treatment for Cycles 4, 5 and 6 will be assessed following the
3rd Cycle. Subjects who have achieved at least stable disease with acceptable toxicity
following 3 Cycles of treatment will be eligible to continue to receive study treatments for
a maximum of 3 further Cycles. In case of progressive disease, at, or at any time after the
start of Cycle 4, subjects must discontinue further study treatment and move into the
study's follow-up period.
During the treatment phase, all eligible subjects will be allocated to receive the following
study treatments:
1. Subjects with Untreated CLL: Up to 6 monthly intravenous infusions of ofatumumab (Cycle
1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 Days)
in combination with up to 6 Cycles of intravenously infused bendamustine (90 mg/m2,
Days 1 and 2, every 28 Days).
2. Subjects with Relapsed CLL: Up to 6 monthly intravenous infusions of ofatumumab (Cycle
1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 Days)
in combination with up to 6 Cycles of intravenously infused bendamustine (70 mg/m2,
Days 1 and 2, every 28 Days).
The studies primary endpoint is overall response rate (ORR) as determined by Investigator
evaluation. The ORR is the percentage of subjects achieving an objective response (i.e.,
partial response or better), using the IWCLL updated NCI-WG guidelines. Response assessments
are planned at the following time-points: After 3 Cycles of ofatumumab plus bendamustine
treatment, after 6 Cycles of ofatumumab plus bendamustine treatment and after the last dose,
if not after 6 cycles, of ofatumumab plus bendamustine treatment.
Follow-up assessments will be performed every 3 months following the last study treatment.
The follow-up period will last for a maximum of 3 years. Response evaluation assessments to
determine subject response or progression will be performed during the follow-up period,
according to the IWCLL updated NCI-WG guidelines. Following progression, only survival
status and details concerning the subject's next CLL therapy will be recorded.
This is a Phase II, open label, single arm, multi-centre study investigating the safety and
efficacy of ofatumumab plus bendamustine in subjects with untreated or relapsed CLL.
The primary objective of this study is to evaluate the investigator assessed overall
response rate (ORR), using the International Workshop for Chronic Lymphocytic Leukaemia
(IWCLL) updated National Cancer Institute-sponsored Working Group (NCIWG) guidelines, in two
populations i.e., subjects with previously untreated CLL and subjects with relapsed CLL
administered ofatumumab plus bendamustine.
Secondary objectives are to evaluate the overall response rate with computed tomography scan
(CT scan) assessment, complete response rate with and without CT scan assessment,
progression free survival, overall survival, duration of response, safety and tolerability,
disease, prognostic and biological marker correlation with clinical response in the two
populations i.e., subjects with previously untreated CLL and subjects with relapsed CLL
administered ofatumumab plus bendamustine.
Exploratory objectives are to investigate the relationship between genetic variants in host
DNA and the efficacy, safety and/or tolerability of ofatumumab.
Each subject from the screening phase who is willing to participate in the study and is
found eligible according to the inclusion and exclusion criteria will enter the treatment
phase and will receive a maximum of 6 Cycles of study treatment (ofatumumab plus
bendamustine). All subjects will receive 3 Cycles of study treatment (Cycles 1, 2 and 3).
Eligibility to receive study treatment for Cycles 4, 5 and 6 will be assessed following the
3rd Cycle. Subjects who have achieved at least stable disease with acceptable toxicity
following 3 Cycles of treatment will be eligible to continue to receive study treatments for
a maximum of 3 further Cycles. In case of progressive disease, at, or at any time after the
start of Cycle 4, subjects must discontinue further study treatment and move into the
study's follow-up period.
During the treatment phase, all eligible subjects will be allocated to receive the following
study treatments:
1. Subjects with Untreated CLL: Up to 6 monthly intravenous infusions of ofatumumab (Cycle
1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 Days)
in combination with up to 6 Cycles of intravenously infused bendamustine (90 mg/m2,
Days 1 and 2, every 28 Days).
2. Subjects with Relapsed CLL: Up to 6 monthly intravenous infusions of ofatumumab (Cycle
1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 Days)
in combination with up to 6 Cycles of intravenously infused bendamustine (70 mg/m2,
Days 1 and 2, every 28 Days).
Prior to each treatment Cycle, subjects must have an absolute neutrophil count > 1.0 x
109/L, a platelet count > 75 x 109/L, and must have recovered to Grade 1 or baseline from
all clinically significant non-hematologic toxicities, other than nausea, vomiting or
alopecia. If these retreatment criteria are not met, a treatment delay of up to 28 Days is
permitted; thereafter, study treatment with bendamustine and ofatumumab must be
discontinued. In cases of delays up to 14 Days, bendamustine treatment should be continued
at the same dosage, but in case of a delay between 15-28 Days, the dosage of bendamustine
must be reduced to 60 mg/m2 for all subsequent treatment Cycles for subjects recruited to
the study with previously untreated CLL and 50 mg/m2 for all subsequent treatment Cycles for
subjects recruited to the study with relapsed CLL.
Additionally, if within any Cycle, a subject develops a clinically significant Grade 3/4
non-hematologic toxicity, other than nausea, vomiting or alopecia, an absolute neutrophil
count < 1.0 x 109/L, or a platelet count < 50% of the pre-treatment value, the bendamustine
dose will also be reduced as stated above for all subsequent treatment Cycles.
Blood samples, lymph node examination, spleen and liver measurements, and constitutional
symptom evaluations are performed monthly throughout the treatment phase. A bone marrow
examination is required to confirm complete response (CR) at least two months after the
final study treatment and when a subject fulfils the IWCLL updated NCI-WG requirements for
CR. CT-Scans will also be performed, at least two months after the final study treatment,
for subjects achieving a CR or partial response (PR) according to the IWCLL updated NCI-WG
requirements. Follow-up assessments will be performed every 3 months following the last
study treatment. The follow-up period will last for a maximum of 3 years. Response
evaluation assessments to determine subject response or progression will be performed during
the follow-up period, according to the IWCLL updated NCI-WG guidelines [Hallek, 2008].
Following progression, only survival status and details concerning the subject's next CLL
therapy will be recorded.
;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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