Prospective Trial on Immunochemotherapy Plus Autologous Stem Cell Transplantation (SCT) and Allogenic SCT in Primary Mantle-Cell-Lymphoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Prospective Phase II Trial on R-CHOP Followed by High-dose BEAM and Autologous SCT and HLA-identical Allogenic SCT After Dose-reduced Conditioning in Patients Age < 55 Years With Primary Mantle-Cell-Lymphoma

Conditions
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Mantle-Cell Lymphoma

Intervention / Treatment
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* Drug: Immunochemotherapy
* Drug: High-dose BEAM plus autologous SCT
* Other: HLA-identical allogenic SCT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First diagnosis of Mantle-Cell-Lymphoma without any previous therapies except for pre-phase treatment consisting of steroids Age 18 to 55 years Confirmed CD20-expression on lymphocytes Effective methods of contraception and negative pregnancy test Sufficient compliance Written patient´s informed consent Exclusion Criteria: Manifest cardiac insufficiency, not compensated Congestive Cardiomyopathy Chronic pulmonary disease including hypoxemia Severe hypertension, not condensable with drugs Severe diabetes mellitus not condensable with drugs Renal Insufficiency ( serum creatinin > 2,0 mg/dl, other than Lymphoma related) Liver impairment ( Transaminases value more than 3 x upper normal value or Bilirubin > 2,0 mg/dl, other than Lymphoma related) HIV-Infection Active Hepatitis B-Infection if continuous virostatic treatment is not possible Active Hepatitis C-Infection Clinical signs of cerebrovascular insufficiency or cerebral damages Pregnancy, lactation or inadequate contraception in women of childbearing age Severe psychiatric disorders Transplantation in the past

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Immunochemotherapy|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|
|Drug: High-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|
|Other: HLA-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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: ORR, OS, EFS |  | during treatment and on day 720 after allogenic SCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity according to WHO-Grading |  | During treatment and until follow-up | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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