To determine the efficacy of two dose regimens of HuMax-CD20 in patients with Follicular Lymphoma who are refractory to rituximab in combination with chemotherapy or to rituximab given as maintenance treatment.
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 6 month period from start of treatment
assessed by an Independent endpoints Review Committee (IRC) according to
the standardized response criteria for Non-Hodgkin*s Lymphomas.
Secondary outcome
1. Duration of response
2. Progression Free Survival (PFS)
3. Time to next FL therapy
4. Overall survival
5. Reduction in tumor size
6. CD19+ and CD20+ cells in peripheral blood
7. Conversion from BCL2 positive to BCL2 negative in peripheral blood (by PCR)
8. Prognostic value of Fc *receptor polymorphism, FLIPI (Follicular
Lymphoma International Prognostic Index) and C1qA-276 mutation
9. Adverse Events
10. Human Anti Human Antibodies (HAHA)
11. Complement: CH50
12. Pharmacokinetic (PK) profile: AUC, Cl, Cmax, Cmin, Tmax, T*, Vz
Background summary
The standard of care for patients with stage III or IV FL has changed
considerably during the recent years. Today, most centers use rituximab in
combination with chemotherapy in first line. Obviously, less toxic treatments,
e.g. novel monoclonal antibodies, might be of value for patients that relapse
on or shortly after rituximab-containing chemotherapy regimens, i.e. rituximab
refractory patients.
Study objective
To determine the efficacy of two dose regimens of HuMax-CD20 in patients with
Follicular Lymphoma who are refractory to rituximab in combination with
chemotherapy or to rituximab given as maintenance treatment.
Study design
double-blind, randomized, two-dose-arm, parallel group, international, multi-
center trial
Intervention
Administration of HuMax-CD20
Study burden and risks
This is a double-blind, randomized, two-dose-arm, parallel group, phase III
trial.
At screening, a physical examination, CT scans, a bone marrow biopsy, if
necessary an excisional lymph node biopsy and a full blood analysis are done to
evaluate the patient for eligibility in the trial. If the patient gives a
separate consent, a fine needle aspirate from an involved lymph node will be
performed as well.
The patient will be randomized to one of the two Humax-CD20 dose arms (500 or
1000 mg), as soon as the patient is evaluated to be eligible for the trial and
has given informed consent.
During the treatment period, each patient will receive eight weekly infusions
of Humax-CD20. The first infusion in both dose arms will be 300 mg, followed by
7 weekly infusions of 500 or 1000 mg.
If the patient has given a separate consent, a fine needle aspirate from an
involved lymph node will be repeated at Week 8.
Disease status will be assessed at Month 3, 6, 9, 12, 18 and 24, including
physical examination, CT scans and a full blood analysis. Evaluation of
response will be done at Month 3, 6, 9, 12, 18 and 24.
Burden and risks for the patient in this trial are comparable to the ones the
patient would have with other treatment such as for example with Rituximab.
A second bone marrow biopsy will be performed immediately after onset of CR or
CRu (as judged
by the investigator) and only in case the screening biopsy was positive for
CD20+ lymphoma as assessed by the central pathologist.
After Month 24, the patients will be monitored for CD19+ and CD20+ cells until
normal range or until a value * the baseline value or until initiation of
alternative FL treatment or Month 60. Patients will be followed until
initiation of alternative FL treatment at 6-months intervals until Month 60.
The evaluation of response will be done centrally and blinded by an IRC.
Toldbodgade 59B
DK-1253 Copenhagen K
DK
Toldbodgade 59B
DK-1253 Copenhagen K
DK
Listed location countries
Age
Inclusion criteria
diagnosis of Follicular Lymphoma grade 1* 2 refractory to rituximab in combination with chemotherapy or to rituximab given as maintenance treatment
Exclusion criteria
The most important exclusion criteria consist of allogenic stem cell transplantation at any time, autologous stem cell transplantation within 6 months prior to Visit 1, more than 1 previous cycle of radio immunotherapy, anticancer therapy or corticosteroid therapy within 4 weeks prior to Visit 1 or known or suspected transformation of the follicular lymphoma to aggressive lymphoma unless new biopsy confirms FL.
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 | EUCTR2006-001433-17-NL |
| CCMO | NL12422.018.06 |