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

Mantle-Cell Lymphoma Clinical Trial

— HD-MCL2003  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00946374
• Other study ID #: L-149/2003
• Secondary ID: BfArM: A-7140-00
• Status: Recruiting
• Phase: Phase 2
• First received: July 24, 2009
• Last updated: July 24, 2009
• Start date: July 2004
• Est. completion date: June 2011

Study information

• Verified date: July 2009
• Source: Heidelberg University
• Contact: Markus Munder, M. D.
• Phone: 0049 6221 56
• Email: markus.munder[@]med.uni-heidelberg.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle-Cell Lymphoma

Intervention

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
• 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.

Locations

Country	Name	City	State
Germany	University Hospital	Heidelberg

Sponsors (1)

Lead Sponsor	Collaborator
Heidelberg University

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: ORR, OS, EFS		during treatment and on day 720 after allogenic SCT	Yes
Secondary	Toxicity according to WHO-Grading		During treatment and until follow-up	Yes
Secondary	GvL-effect after allogenic SCT		Allogenic SCT until day 720 after transplantation	Yes
Secondary	Comparison of OS between patients completing the protocol and patients not receiving allogenic SCT		First diagnosis of MCL until day 720 after transplantation	No

External Links

•   Homepage University hospital Heidelberg, Germany