Mantle-Cell Lymphoma
Conditions
Keywords
Mantle-Cell-Lymphoma, MCL, Non Hodgkin´s Lymphoma, NHL, Immunochemotherapy, R-CHOP, CHOP, High-dose chemotherapy, BEAM, HD-BEAM, Autologous stem cell transplantation, Reduced conditioning regimen, Unrelated donor, Sibling donor, Total Body Irradiation, TBI, Allogenic stem cell transplantation, ABSCT, ASCT, Fludarabine+TBI
Brief summary
The purpose of this study is to improve the overall survival of Mantle-Cell-Lymphoma (MCL) by a new concept of treatment with primary curative intention consisting of six courses of immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (SCT) and HLA-identical allogenic SCT after a dose-reduced conditioning regimen of total body irradiation (TBI) with 2 Gy and Fludarabine in younger patients with primary Mantle-Cell-Lymphoma
Detailed description
With a median overall survival of approximately 3 years, MCL has the poorest prognosis of all NHL entities. No potentially curative therapy has been established yet as even more intensive therapies including high-dose chemotherapy plus autologous SCT show only moderate improvement of the prognosis of MCL. Allogenic SCT seems to have an immunological mechanism of action in NHL, which is commonly known as Graft-versus-Lymphoma effect. This trial´s purpose is to improve the overall survival in patients younger than 55 years with primary MCL by sequentially combining autologous SCT and allogenic SCT after the application of 6 courses of immunochemotherapy and high-dose chemotherapy.
Interventions
R-CHOP: Rituximab 375 mg/m²,intravenous ( iv ), day 0 ; Cyclophosphamide 750 mg/m²,iv, day1; Vincristine 1,4 mg/m² but at the maximum 2 mg,iv,d1; Doxorubicin 50 mg/m², iv, d1; Prednisone 100 mg, peroral ( po ), day 1 to day 5
DRUGHigh-dose BEAM plus autologous SCT
High-dose BEAM: Carmustine 300mg/m², iv, day -7; Cytarabine 2 x 200 mg/m², iv, day -6 to day -3; Etoposide 2 x 100 mg/m², iv, day -6 to day -3; Melphalan 140 mg/m², iv, day -2 followed by Autologous stem cell transplantation ( \> 2,5 x 10e6 CD34 positive autologous stem cells, iv, day 0
OTHERHLA-identical allogenic SCT
Fludarabine 30 mg/m², iv, day -4 to day -2; Cyclosporin A 2 x 3mg/kg, iv, day -1 to day 0 plus total body irradiation with 2 Gy, day 0 followed by allogenic stem cell transplantation immediately after Radiation.
Sponsors
Heidelberg University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. First diagnosis of Mantle-Cell-Lymphoma without any previous therapies except for pre-phase treatment consisting of steroids 2. Age 18 to 55 years 3. Confirmed CD20-expression on lymphocytes 4. Effective methods of contraception and negative pregnancy test 5. Sufficient compliance 6. Written patient´s informed consent
Exclusion criteria
1. Manifest cardiac insufficiency, not compensated 2. Congestive Cardiomyopathy 3. Chronic pulmonary disease including hypoxemia 4. Severe hypertension, not condensable with drugs 5. Severe diabetes mellitus not condensable with drugs 6. Renal Insufficiency ( serum creatinin \> 2,0 mg/dl, other than Lymphoma related) 7. Liver impairment ( Transaminases value more than 3 x upper normal value or Bilirubin \> 2,0 mg/dl, other than Lymphoma related) 8. HIV-Infection 9. Active Hepatitis B-Infection if continuous virostatic treatment is not possible 10. Active Hepatitis C-Infection 11. Clinical signs of cerebrovascular insufficiency or cerebral damages 12. Pregnancy, lactation or inadequate contraception in women of childbearing age 13. Severe psychiatric disorders 14. Transplantation in the past
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy: ORR, OS, EFS | during treatment and on day 720 after allogenic SCT |
Secondary
| Measure | Time frame |
|---|---|
| GvL-effect after allogenic SCT | Allogenic SCT until day 720 after transplantation |
| Comparison of OS between patients completing the protocol and patients not receiving allogenic SCT | First diagnosis of MCL until day 720 after transplantation |
| Toxicity according to WHO-Grading | During treatment and until follow-up |
Countries
Germany
Contacts
Primary ContactMarkus Munder, M. D.
Outcome results
None listed