Primary: To evaluate the efficacy and safety of HuMax-CD20 in patients with B-cell Chronic Lymphocytic Leukemia (B-CLL) who have failed fludarabine and alemtuzumabSecondary: To determine the host immune response to HuMax-CD20To determine the…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's B-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Objective response as measured over a 24 week period from start of treatment
assessed by an Independent endpoints Review Committee (IRC) according to the
NCIWG guidelines
Secondary outcome
Duration of response, Progression Free Survival (PFS), Time to next B-CLL
therapy, Overall survival, Reduction in tumor size, CD5+CD19+, CD5+CD20+ in
peripheral blood, and expressions of CD19, CD20, CD55 and CD59 on CD45+CD5+
cells, Constitutional symptoms (B-symtoms), Resolution of lymphadenopathy,
Resolution of organomegaly,
Prognostic value of FISH-parameters, CD38+, VH mutational status, FC receptor
polymorphisms, C1qA-276 mutation, β2 microglobulin, thymidin kinase,
circulating CD20, antigen density,
Improvement in ECOG Performance Status, Improvement in hemoglobin, Improvement
in thrombocytopenia, Improvement in neutropenia, Number of blood transfusions,
Number of grade 3 and 4 infections, Number of autoimmune hemolysis
Background summary
Patients failing fludarbine and alemtuzumab have currently no available
treatments options. HuMax CD20 is a fully human antibody which might meet this
unmet medical need.
Study objective
Primary:
To evaluate the efficacy and safety of HuMax-CD20 in patients with B-cell
Chronic Lymphocytic Leukemia (B-CLL) who have failed fludarabine and alemtuzumab
Secondary:
To determine the host immune response to HuMax-CD20
To determine the pharmacokinetic profile of HuMax-CD20
Study design
international, multicenter, signle-arm, open
Intervention
Each patient will receive eight weekly infusions of HuMax-CD20, followed by 4
monthly infusions of HuMax-CD20.
Study burden and risks
At screening, different blood samples, a physical examination, a CT scan and a
bone marrow examination are done and the patient is evaluated for eligibility
in the trial.
Disease status will be assessed every 4 weeks until Week 28, including physical
examination, spleen and liver measurement, and blood samples.
A CT scan and a bone marrow examination will be performed for confirmation 8
weeks after a patient, for the first time, fulfills the NCIWG requirements of a
CR.
After Week 28, disease status evaluation (physical examination, spleen and
liver measurement, and blood samples) will take place every 3 months until
disease progression or until Month 24.
Hereafter, the patients will be monitored for CD5-CD19+ and CD5-CD20+ cells
until one value >= the baseline value or until alternative B-CLL treatment or
Month 48. Patients will be followed for survival at 3-months intervals until
Month 48.
The evaluation of response will be done centrally by an IRC. Evaluation of
response will be done at Visit 6 and from Visit 10 to 21.
In regard to burden and risks does this trials have no difference than the
patient would have with other treatment such as for example Rituximab.
Toldbodgade 59B
DK-1253 Copenhagen K
Denmark
Toldbodgade 59B
DK-1253 Copenhagen K
Denmark
Listed location countries
Age
Inclusion criteria
The trial population will be comprised of patients with a diagnosis of B-CLL who have failed both fludarabine and alemtuzumab and who have active disease.;Active B-CLL is defined and confirmed according to the NCIWG guidelines and with an indication for treatment.;Failing at least one fludarabine-containing treatment regimen is defined as:
1. Refractory to one fludarabine -containing treatment regimen, defined as:
a. failure to achieve at least PR to at least one fludarabine-containing treatment regimen;
or,
b. disease progression while on a fludarabine-containing treatment regimen; or,
c. disease progression in responders within 6 months of the last dose of a fludarabine- containing treatment regimen;2. Intolerant to fludarabine, defined as:
a. Discontinuation of therapy due to side effects/toxicity whether or not response occurred;
or
b. Ineligible to treatment with fludarabine due to history of previous fludarabine-induced autoimmune hemolytic anemia or autoimmune thrombocytopenia;Failing at least one alemtuzumab-containing treatment regimen is defined as:
1. Refractory to one alemtuzumab-containing treatment regimen, defined as:
a. failure to achieve at least PR to at least one alemtuzumab-containing treatment regimen;
or,
b. disease progression while on a alemtuzumab-containing treatment regimen; or,
c. disease progression in responders within 6 months of the last dose of a alemtuzumab- containing treatment regimen
2. Intolerant to alemtuzumab, defined as:
a. Discontinuation of therapy due to side effects/toxicity whether or not response occurred;
or,
b. Ineligible to treatment with alemtuzumab due to concurrent medical conditions, such as:
i. previous pneumocystis carinii pneumonia (PCP) ii. history of other severe opportunistic infections iii. repeated grade 3 or 4 infections of other types
iv. lympadenopathy with at least one lymph node > 5 cm causing symptoms or compression and requiring therapy;A patient must have failed at least one fludarabine-containing treatment regimen and one alemtuzumab-containing treatment regimen, as defined above. Patients must have an ECOG Performance Status of 0, 1 or 2 and a life expectancy of at least 4 months.;The patients should be >= 18 years of age and have given informed consent.
Exclusion criteria
The most important exclusion criteria consist of previous treatment with alemtuzumab within 6 weeks prior to Visit 1, previous autologous stem cell transplantation within 6 months prior to Visit 1, allogenic stem cell transplantation at any time, radioimmunotherapy at any time or anticancer therapy within 4 weeks prior to Visit 1 and known or suspected transformation of B-CLL.
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 |
|---|---|
| EudraCT | EUCTR2005-006163-31-NL |
| CCMO | NL11928.078.06 |