Patients with relapsed or primary progressive aggressive non-Hodgkin's lymphoma. These lymphomas comprise: 1. Follicular lymphoma grade III (FL III°) 2. Diffuse large B cell lymphoma (DLBCL), all variants and subtypes including primary mediastinal B-NHL 3. Mantle cell lymphoma (MCL), blastoid variant 4. Burkitt lymphoma (BL) 5. aggressive marginal zone lymphoma (MZL)
Conditions
Interventions
Trade Name: Revlimid
Product Name: Lenalidomide
Product Code: Lenalidomide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Current Sponsor code: Lenalidomi
Sponsors
GMIHO Gesellschaft für Medizinische Innovation-Hämatologie und Onkologie mbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age: 18-70 years 2. Risk group: All risk groups 3. Histology: Diagnosis of a relapsed or primary progressive aggressive non-Hodgkin's lymphoma. These lymphomas comprise: - Follicular lymphoma grade III (FL III°) - Diffuse large B cell lymphoma (DLBCL), all variants and subtypes including primary mediastinal B-NHL - Mantle cell lymphoma (MCL), blastoid variant - Burkitt lymphoma (BL) - aggressive marginal zone lymphoma (MZL) 4. Performance status: Performance status ECOG 0 - 2 5. Female subjects of childbearing potential must: - Understand the study drug is expected to have a teratogenic risk - Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout the entire duration of study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhoea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception - Implant - Levonorgestrel-releasing intrauterine system (IUS) - Medroxyprogesterone acetate depot - Tubal sterilisation - Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses - Ovulation inhibitory progesterone-only pills (i.e., desogestrel) - If not established on effective contraception, the female subject must be referred to an appropriately trained health care professional for contraceptive advice in order that contraception can be initiated. - Because of the increased risk of venous thromboembolism in patients with multiple myeloma taking lenalidomide and dexamethasone, combined oral contraceptive pills are not recommended. If a female subject is currently using combined oral contraception the patient should switch to one of the effective method listed above. The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception. The efficacy of contraceptive steroids may be reduced during co-treatment with dexamethasone. - Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics should be considered particularly in patients with neutropenia. - Copper-releasing intrauterine devices are generally not recommended due to the potential risks of infection at the time of insertion and menstrual blood loss which may compromise patients with neutropenia or thrombocytopenia. - Understand that even if she has amenorrhea, she must follow all the advice on effective contraception - She understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy. - Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml on the day of the study visit or in the 3 days prior to the study visit once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence. The test should ensure the subject is not pregnant when she starts treatment. - Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal s
Exclusion criteria
Exclusion criteria: Key exclusion criteria: 1. Pregnant or lactating females 2.Already initiated salvage lymphoma therapy (except for the prephase treatment specified for this study) 3. Serious accompanying disorder or impaired organ function causing significant clinical problems and reduced life expectancy, in particular: 3.1.heart: angina pectoris CCS >2, cardiac failure NYHA >2 and/or EF 2 times the upper reference limit 3.4.liver: bilirubin > 2 times the upper reference limit 4. Platelets 25% 6. Known hypersensitivity to the medications to be used 7. Known HIV-positivity 8. Suspicion that patient compliance will be poor especially that rules for effective contraception may not be followed. 9. Simultaneous participation in other treatment studies 10. Non-conformity to eligibility criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the maximal applicable dose of lenalidomide given together with a standard salvage regimen (R-DHAP: rituximab, dexamethason, cytarabine and cisplatinum) for treatment of relapsed and primary progressive NHL. Estimation of efficacy and toxicity of this regimen for this patient population;Secondary Objective: To provide efficient remission induction in second line treatment of aggressive NHL giving a higher fraction of patients the chance to achieve remission and subsequently to receive salvage therapy (autologous or allogeneic SCT). To achieve better overall and progression free survival in patients with relapsed and primary progressive aggressive NHL.;Primary end point(s): Primary end points a) Maximal tolerable dose (MTD) of lenalidomide given in combination with standard R-DHAP b) Overall response rate (CR/CRu, PR) achievable with MTD R2-DHAP Secondary end points Rate of complete remission (CR), rate of primary progression, relapse rate, rate of treatment-related deaths, overall survival (OS), progression-free survival (PFS), event-free survival (EFS), tumour control, feasibility of stem cell mobilization, incidence of non-hematological toxicities > grade 2 CTC, incidence and duration of neutropenia and thrombopenia grade 4 | — |
Countries
Germany
Outcome results
None listed