To demonstrate in a phase III study that the addition of the monoclonal anti-T cell antibody alemtuzumab added to standard CHOP chemotherapy followed by autologous stam cell transplantation will increase the response, event-free survival,…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's T-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Event-free survival at 3 yr
Secondary outcome
overall survival at 3 yr
progression-free survival at 3 yr
responses (%CR and %PR), at the end of therapy
time to progression
relation CD52 expression and response-rate
safety addition of alemtuzumab to CHOP measured by incidences of infections
Background summary
The prognosis of patients with peripheral T cell lymphoma is poor despite
optimal CHOP-like chemotherapy. In patients with B cell lymphoma, the addition
of the B cell monoclonal antibody rituximab to CHOP chemotherapy resulted in a
10-15% survival improvement in both elderly and younger patients. Here, the
efficacy and toxicity of the monoclonal anti-T cell antibody alemtuzumab will
be studied in a randomized phase III trial. Alemtuzumab will be added to the
standard therapy consisting of CHOP chemotherapy followed by consolidating
autologous stem cell transplantation (standard arm), since several phase II
studies consisting of the combination of alemtuzumab with CHOP showed promising
responses with acceptable toxicity. If the addition of alemtuzumab is indeed
successful as studied in this phase III setting, this monoclonal antibody will
be added to all patients with T cell lymphoma who are candidate for intensive
therapy.
Study objective
To demonstrate in a phase III study that the addition of the monoclonal anti-T
cell antibody alemtuzumab added to standard CHOP chemotherapy followed by
autologous stam cell transplantation will increase the response, event-free
survival, progression-free survival and overall survival, without unacceptable
additional toxicity.
Study design
Multicenter randomized phase III trial, see above
Intervention
the addition of alemtuzumab to standard CHOP-14 followed by autologous
transplant
Study burden and risks
Standard induction treatment consists of CHOP, given at 2 weeks interval. The
addition of alemtuzumab requires subcutaneous injections at day 1 and 2. The
first 2 injections can cause transient painful infiltrates. The risk on
infections is increased requiring additional antibiotics and blood controls,
especially related to CMV re-activations. Blood products need to be irradiated.
Aarhus University Hospital Tage Hansens Gade 2
8000
DK
Aarhus University Hospital Tage Hansens Gade 2
8000
DK
Listed location countries
Age
Inclusion criteria
1. Age: 18-65 years
2. All stages, including stage I with bulk (>= 7.5 cm)
3. Confirmed histological diagnosis of peripheral T cell NHL of the following types:
peripheral T-cell lymphoma PTCL-NOS
Angioimmunoblastic T cell lymphoma
Anaplastic large cell lymphoma, only if primary systemic and ALK-negative
intestinal T/NK-cell lymphoma (± enteropathy)
hepatosplenic gamma-delta lymphoma
subcutaneous panniculitis-like PTCL
extranodal NK/T cell lymphoma, nasal type
4. Performance status: ECOG 0 - 2 (Karnofsky index: 60 - 100%). ECOG 3 is acceptable, if lymphoma related.
5. Measurable disease
6. written consent of the patient
7. life expectancy of 3 months or longer
Exclusion criteria
1. Stage I with IPI 0 and without bulk
2. Already initiated lymphoma therapy
3. Serious accompanying disorder or impaired organ function, in particular:
- severe cardiac dysfunction (NYHA class II-IV; LVEF <45%)
- severe pulmonary dysfunction (FeV1<50% or DC <50%)
- Renal: creatinine >150 umol/l, unless related to NHL
- Hepatic: bilirubin >2.5 times the upper reference limit, unless related to NHL
- Uncontrollable diabetes mellitus (prephase treatment with prednisone!)
4. T-cell malignanies of other categories
5. CNS involvement
6. Known hypersensitivity to the medications to be used, especially murine or
chimeric antibodies
7. uncontrolled asthma or allergy
8. Known HIV-positivity
9. Active hepatitis infection, active CMV infection, active systemic fungal infection,
active infection with mycobacterium tuberculosis or atypical tuberculosis
10. Suspicion that patient compliance will be poor
11. Simultaneous participation in any other study protocol
12. Prior chemo- or radiotherapy for malignancy
13. Other concomitant malignant disease (history of active cancer during the past 5
years, except basal carcinoma of the skin or stage 0 cervical carcinoma)
14. Non-conformity to eligibility criteria
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 | EUCTR2006-006130-17-NL |
| CCMO | NL18525.042.08 |