The primary objective is to evaluate progression free survival (PFS) of ofatumumab maintenance treatment versus no further treatment after remission induction in subjects with relapsed CLL.Secondary objectives are to evaluate clinical benefit,…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression free survival (PFS), defined as the interval from randomization
until disease progression or death
Secondary outcome
Improvement in response
Time to next treatment
Overall survival
Quality of Life
Effectivity and safety of Ofatumumab
prognostic markers in respons to clinical outcome
Pharmacokinetics of Ofatumumab
Background summary
Despite progress in therapy, chronic lymphocytic leukemia (CLL) remains
incurable. Response rates are promising but remain transient and all subjects
eventually relapse. There is currently no approved maintenance therapy. The
objective of this study is to evaluate if maintenance therapy with ofatumumab
will prolong remission duration.
The purpose of this study is to assess the benefit of ofatumumab maintenance
treatment in subjects in remission from relapsed CLL based upon:
1) the similarities in biological behavior between CLL and FL;
2) in relapsed FL, maintenance treatment with anti-CD20 MAb, rituximab is the
standard of care;
3) results in a phase II study with rituximab induction and maintenance
resulted in prolongation of PFS in MRD positive CLL in first remission after
fludarabine;
4) ofatumumab has higher in vitro activity against CLL cells; and
5) ofatumumab has also demonstrated efficacy in relapsed CLL as monotherapy
(Study Hx-CD20-406).
Study objective
The primary objective is to evaluate progression free survival (PFS) of
ofatumumab maintenance treatment versus no further treatment after remission
induction in subjects with relapsed CLL.
Secondary objectives are to evaluate clinical benefit, safety, tolerability and
health-related quality of life of subjects treated with ofatumumab versus no
further treatment. An additional secondary objective is to evaluate the
pharmacokinetics in CLL subjects on maintenance ofatumumab.
Study design
This is an open-label, two-arm, randomized, Phase III study of ofatumumab or no
further treatment in subjects in CR or PR after remission induction treatment
for relapsed CLL.
Eligible subjects will be stratified at randomization based on:
1) CR or PR at study entry
2) Number of previous induction treatments (2 vs 3)
3) Type of prior treatment : chemoimmunotherapy, only alkylating monotherapy,
or other treatment
During the treatment phase, subjects will be randomized 1:1 to receive either:
Arm A: ofatumumab as infusions every 8 weeks (The first dose will be 300mg
followed 1 week later by 1000 mg and 1000 mg every 8 weeks thereafter for up to
2 years) or
Arm B: No treatment (i.e. observation only)
Intervention
n.a.
Study burden and risks
n.a.
Huis ter Heideweg 62
3705 LZ Zeist
NL
Huis ter Heideweg 62
3705 LZ Zeist
NL
Listed location countries
Age
Inclusion criteria
- Adults with documented diagnosis of CLL based on the modified IWCLL updated NCI-WG guidelines [Hallek, 2008]
- CR or PR according to the revised 2008 NCI-WG CLL criteria, confirmed by CT scan, after 2nd/3rd line treatment
- The anti-leukemic treatment before study entry should have been at least 4 months of monotherapy with alkylating agents and/or at least 4 consecutive cycles of polychemotherapy (e.g. CVP), fludarabine-containing chemotherapy or immunochemotherapy
- ECOG Performance Status of 0-2
- Signed written informed consent
Exclusion criteria
- Primary or secondary fludarabine-refractory subjects, defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months of last anti-leukemic therapy [Hallek, 2008]
- Prior maintenance therapy
- Known transformation of CLL (e.g. Richter*s transformation)
- Known prolymphocytic leukemia (PLL)
- Known 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
- Other past or current malignancy
- Clinically significant cardiac disease
- History of significant cerebrovascular disease or event with symptoms or sequelae
- Glucocorticoid unless given in doses <= 100 mg/day hydrocortisone (or equivalent dose of other glucocorticoid) if for exacerbations other than CLL (e.g. asthma)
- Known HIV positive
- Known or suspected hypersensitivity to ofatumumab
- 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
- Subjects known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
- 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov |
| EudraCT | EUCTR2009-012518-39-NL |
| CCMO | NL30218.018.10 |