The goal of this study is to evaluate efficacy and safety of the combination of lenalidomide, an immunomodulatory drug (IMiD) with a standard immunochemotherapy treatment, called R-DHAP. R-DHAP consists of a monoclonal antibody called Rituximab and chemotherapy consisting of Dexamethasone, high dose Cytarabine, often called Ara-C, and platinum based chemotherapy, either cisplatinum, or, if treatment with cisplatinum is contraindicated, carboplatinum.
This is a phase 1/2 study to evaluate the efficacy and safety of lenalidomide added to a standard chemotherapy regime of R-DHAP (Rituximab, Dexamethasone, high-dose Cytarabine, Cis/Carboplatinum) in the treatment of relapsed or refractory high-grade B-cell non-hodgkin-lymphoma (NHL). The study hypothesis is that the combination of lenalidomide with standard immunochemotherapy will lead to an overall response rate of at least 60%. In this study, 3 rounds of immunochemotherapy in combination with lenalidomide will be administered. After the first or second round of therapy, peripheral hematopoetic stem cells will be harvested. Consolidation treatment with autologous or allogenic peripheral blood stem cell transplantation is recommended in all patients suitable, but is not part of the study. In phase 1, up to six cohorts of at least 6 patients each will be treated with the study therapy, with lenalidomide in increasing dosages, to determine the maximum tolerated dose (MTD). In phase 2, 50 patients will be treated with the MTD. Efficacy and safety will be evaluated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Rituximab 375 mg/m²
Cisplatinum 100 mg / m²
Carboplatinum AUC5
Dexamethasone 40 mg
Cytarabine 2000 mg/m², administered twice
5-20 mg administered either d1-d7, or d-6-d7
PegFilgrastim 6 mg
collection of peripheral stem cells for autologous stem cell transplantation
Diakonie Krankenhaus Bremen
Bremen, Germany
Klinikum Chemnitz
Chemnitz, Germany
Universitätsklinikum Essen
Essen, Germany
Klinikum Frankfurt/Oder
Frankfurt (Oder), Germany
Universitätsklinikum Göttingen
Göttingen, Germany
Asklepios Klinik St. Georg
Hamburg, Germany
Asklepios Klinik Altona
Hamburg, Germany
Universitätsklinikum Heidelberg
Heidelberg, Germany
Universitätsklinikum des Saarlandes
Homburg, Germany
Westpfalz Klinikum
Kaiserslautern, Germany
...and 2 more locations
Overall Response Rate (ORR)
The percentage of patients which showed either a partial remission (PR), a complete remission with remaining uncertainty (CRu) or a complete remission (CR) after study treatment.
Time frame: 78 - 85 days + 2 years Follow Up
Maximum tolerated dose (MTD)
The maximum dose of lenalidomide tolerated with acceptable toxicity during phase 1 of this study. The MTD established in phase 1 of this study will be administered to 50 patients in phase 2 of this study.
Time frame: 78 - 85 days
Rate of complete remission
laboratory, BM biopsy, imaging
Time frame: 78 - 85 days + 2 years Follow Up
Rate of primary progression
The rate of patients which show progressive disease (PD) during or directly after study therapy
Time frame: 78 - 85 days + 2 years Follow Up
Rate of treatment related deaths
check survival
Time frame: 78 - 85 days + 2 years Follow Up
Relapse Rate
laboratory, BM biopsy, imaging
Time frame: 78 - 85 days + 2 years Follow Up
Overall Survival
check survival
Time frame: 78 - 85 days + 2 years Follow Up
Progression free survival
laboratory, BM biopsy, imaging
Time frame: 78 - 85 days + 2 years Follow Up
tumour control
laboratory, BM biopsy
Time frame: 78 - 85 days + 2 years Follow Up
feasibility of stem cell mobilization
The collection of peripheral stem cells is needed to be able to offer the patient high dose chemotherapy followed by autologous stem cell transplantation after the study treatment has ended. Stem cell collection of \<2.0 \*10e6 CD34+cells/kg will be considered insufficient.
Time frame: 78 - 85 days + 2 years Follow Up
incidence of non-hematological toxicities > grade 2 CTC
Time frame: 78 - 85 days + 2 years Follow Up
incidence and duration of neutropenia and thrombopenia grade 4
laboratory WBC \< 1.0 /nl or Plt \< 25 /nl
Time frame: 78 - 85 days + 2 years Follow Up
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