Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00003873

Trial Description

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Title

Improvement of Outcome and Reduction of Toxicity in Elderly Patients With CD20+ Aggressive B-Cell Lymphoma by an Optimised Schedule of the Monoclonal Antibody Rituximab, Substitution of Conventional by Liposomal Vincristine, and FDG-PET Based Reduction of Therapy.

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Trial Acronym

OPTIMAL>60

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URL of the Trial

[---]*

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Brief Summary in Lay Language

The purpose of this study is to improve the outcome of elderly patients with CD20+
Aggressive B-Cell Lymphoma and to reduce the toxicity of standard used Immuno-Chemotherapy
by using an optimised schedule of the monoclonal antibody Rituximab, substituting
conventional by Liposomal Vincristine and by a PET-guided reduction of therapy.

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Brief Summary in Scientific Language

Primary objective of study:

"OPTIMAL>60 Less Favourable" Patients with less favourable prognosis:

1. To test whether progression-free survival (PFS) can be improved by substituting
conventional by liposomal vincristine;

2. To test whether PFS can be improved by 12 optimised applications instead of 8 2-week
applications of rituximab.

"OPTIMAL>60 Favourable": Patients with favourable pro-gnosis:

3. Comparison of neurotoxicity of conventional and liposomal vincristine;

4. Determination of PFS for the treatment strategy of reducing treatment in patients with
negative FDG-PET after 4 x R-CHOP/CHLIP-14 (PET-4) and comparison with the
corresponding patient population in RICOVER-60.

Secondary objectives:

"OPTIMAL>60 Favourable" and "OPTIMAL>60 Less Favourable":

5. Comparison of the prognostic value of a pre-treatment FDG-PET (PET-0) with conventional
CT/MRT.

6. Comparison of the FDG-PET-based individualised treatment strategy in OPTIMAL>60 with
the fixed (pre-defined) treatment strategy in RICOVER>60.

7. Estimation of the vincristine-related neurotoxicity ("OPTIMAL>60 Less Favourable only,
since vincristine related neurotoxicity is primary objective of the study in favourable
patients) and other toxicities (all patients).

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Organizational Data

  •   DRKS00003873
  •   2012/05/11
  •   2011/11/18
  •   yes
  •   [---]*
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Secondary IDs

  •   NCT01478542  (ClinicalTrials.gov)
  •   DSHNHL 2009-1  (University Hospital, Saarland)
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Health Condition or Problem studied

  •   CD20+ Aggressive B-Cell Lymphoma
  •   C85.1 -  B-cell lymphoma, unspecified
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Interventions/Observational Groups

  •   Drug: Conventional Vincristine
  •   Drug: Liposomal Vincristine
  •   Drug: Ricover-scheme rituximab
  •   Drug: optimised rituximab-schedule
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Factorial
  •   III
  •   [---]*
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Primary Outcome

- Progression-free survival; time frame: 9 years; "OPTIMAL>60 Less Favourable": To test the effects of substitution of conventional by liposomal vincristine and of a 2-week applications of 8x rituximab by an optimised application of 12 x rituximab stratified log rank tests will be performed for each question (stratified for IPI-factors). Proportional hazard models will be used to investigate treatment interaction and to obtain estimates for the single treatment effects (HR) adjusting for the IPI-factors.
"OPTIMAL>60 Favourable" Grade of neurotoxicity will be estimated and indicated with a 95% confidence interval (CI) separated to each type of vincristine. To investigate the 3-year PFS with 95% CI the Kaplan-Meier estimator will be used.

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Secondary Outcome

- for efficacy: rate of complete remissions (CR-rate), rate of partial responses (PR-rate), rate of primary progressions, relapse rate, event-free survival (EFS) and overall survival (OS); rate and CTC grades of polyneuropathy.; time frame: 9 years; Secondary endpoints: To analyze how (i. e. in which direction) and how often a pre-treatment FDG-PET-based assignment (PET-0) would have affected the assignment of a patient to a different stage, IPI risk group or treatment, respectively.
To compare the efficacy and side effects of the (post-induction therapy FDG-PET-based) individualised treatment strategy in OPTIMAL>60 with the fixed (pre-defined) treatment strategy in RICOVER-60.
Rates and grades of polyneuropathy will be determined according to CTC-v4.03

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

  •   [---]*
  •   2011/11/30
  •   1152
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   61   Years
  •   80   Years
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Additional Inclusion Criteria

1. Age: 61-80 years

2. All risk groups (IPI 1-5)

3. Diagnosis of aggressive CD20+ B-NHL, based on an excisional biopsy of a lymph node or
on an appropriate sample of a lymph node or of an extranodal involvement. It will be
possible to treat the following entities in this study as defined by the new WHO
classification of 200870:

B-NHL:

- Foll. lymphoma grade IIIb

- DLBCL, not otherwise specified (NOS)

- common morphologic variants:

- centroblastic

- immunoblastic

- anaplastic

- rare morphologic variants

- DLBCL subtypes/entities:

- T-cell/histiocyte-rich large B-cell lymphoma

- primary cutaneous DLBCL, leg type

- EBV-pos. DLBCL of the elderly

- DLBCL associated with chronic inflammation

- primary mediastinal (thymic) LBCL

- intravascular large B-cell-lymphoma

- ALK-positive large B-cell-lymphoma

- plasmoblastic lymphoma

- primary effusion lymphoma

- secondary or simultaneous high grade B-cell-lymphoma

- B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and
Burkitt lymphoma

- B-cell lymphoma, unclassifiable, with features intermediate between DLCBL and
Hodgkin lymphoma

4. Performance status ECOG 0 - 2 after prephase treatment. The performance status of
each patient must be assessed before the initiation and after the end of prephase
treatment which, as experience has shown, can result in a significant improvement of
the patient's performance status. The pre-treatment performance status which can
range from ECOG 0 to ECOG 4 must be documented in the Staging CRF (see ISF); the
performance status after the prephase treatment must be documented in the respective
Prephase Treatment CRF (PT form: see ISF). A definition of the performance status is
provided in Appendix 28.10.

5. Written informed consent of the patient

6. Contract of participation signed by the study centre and sponsor

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Exclusion Criteria

1. Already initiated lymphoma therapy (except for the prephase treatment)

2. Serious accompanying disorder or impaired organ function (except when due to lymphoma
involvement), in particular:

- heart: angina pectoris CCS >2, cardiac failure e.g. NYHA >2 and/or EF <50% or
FS<25% in nuclear medicine examination/echocardiography

- lungs: if respiratory problems are suspected the patient is to be excluded if
the resultant pulmonary function test shows FeV1<50% or a diffusion capacity
<50% of the reference values

- kidneys: creatinine >2 times the upper reference limit

- liver: bilirubin >2 times the upper reference limit, aspartate transaminase
(AST, SGOT) or alanine transaminase (ALT, SGPT) >3 x institutional upper
reference limit

- uncontrollable diabetes mellitus (prephase treatment with predniso[lo]ne!)

3. Platelets <75 000/mm3, leukocytes <2 500/mm3 (if not due to lymphoma)

4. Known hypersensitivity to the medications to be used

5. Known HIV-positivity

6. Patients with severe impairment of immune defense

7. Patients with constipation with imminent risk of ileus

8. Chronic active hepatitis

9. Poor patient compliance

10. Simultaneous participation in other treatment studies or in another clinical trial
within the last 6 months

11. Prior chemo- or radiotherapy, long-term use of corticosteroids or anti-neoplastic
drugs for previous disorder

12. Other concomitant tumour disease and/or tumour disease in the past 5 years (except
basalioma of the skin and carcinoma in situ)

13. CNS involvement of lymphoma (intracerebral, meningeal, intraspinal intradural) or
primary CNS lymphoma

14. Persistent neuropathy grade ≥2 (NCI CTC-AE v4.03) (unless due to lymphoma
involvement)

15. History of persistent active neurologic disorders grade >2 including demyelinating
form of Charcot-Marie-Tooth syndrome, acquired demyelinating disorders, or other
demyelinating condition

16. Pregnancy or breast-feeding women

17. Active serious infections not controlled by oral and/or intravenous antibiotics or
anti-fungal medication

18. Any medical condition which in the opinion of the investigator places the subject at
an unacceptably high risk for toxicities.

19. MALT lymphoma

20. Non-conformity to eligibility criteria

21. Persons not able to understand the impact, nature, risks and consequences of the
trial (including language barrier)

22. Persons not agreeing to the transmission of their pseudonymous data

23. Persons depending on sponsor or investigator

24. Persons from highly protected groups. Pts. with CNS lymphoma should not be included
in this study.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • University Hospital, Saarland
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    •   [---]*
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    • German High-Grade Non-Hodgkin's Lymphoma Study Group
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    •   [---]*
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  • start of 1:1-Block address scientific-contact
    • Saarland University, Saarland University Hospital
    • Michael G. Pfreundschuh, Professor 
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    • DSHNHL Central Study Office 
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    •   +4968411623084
    •   [---]*
    •   DSHNHL at uks.eu
    •   [---]*
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   125
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.