Phase II Open-Label Study on Lenalidomide, Tafasitamab, and Rituximab in Frontline Diffuse Large B-Cell Lymphoma in Patients Aged 80 and Older
- Trial ID
- 2023-507286-25-00
- Protocol
- VERLEN
- Sponsor
- Lysarc
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of the combination of tafasitamab (an anti-CD19 antibody) and lenalidomide, when associated with rituximab (R-Tafa-Len), in elderly patients diagnosed with **Diffuse Large B-Cell Lymphoma**. This is assessed by the Overall Response Rate (ORR) after 3 cycles of treatment or at the point of permanent treatment discontinuation, whichever occurs first. The clinical relevance of this objective lies in its potential to improve therapeutic outcomes in a population that is often underrepresented in clinical trials due to age-related factors.
Secondary objectives include:
- Assessing the safety of lenalidomide and tafasitamab in patients treated with rituximab.
- Evaluating the efficacy of the R-Len-Tafa regimen as measured by 2-year Progression-Free Survival (PFS) and 2-year Overall Survival (OS).
- Evaluating the Overall Response Rate (ORR) and Complete Metabolic Response (CMR) after 3 and 6 cycles, or at permanent treatment discontinuation, based on central review and investigator assessment according to Lugano Response Criteria.
- Assessing the safety of patients who switch to R-miniCHOP, focusing on tafasitamab and/or lenalidomide-related serious adverse events and deaths.
- Evaluating the response to R-miniCHOP, PFS, and OS in patients who switch to this regimen.
- Assessing geriatric quality of life at enrollment, after 3 cycles, and at the end of treatment.
- Investigating the influence of circulating tumor DNA (ctDNA) as an early predictor of therapeutic response.
- Conducting an extensive analysis of the tumor immune microenvironment, focusing on lenalidomide immunomodulation and tafasitamab-induced immune responses.
- Analyzing the immune response in the blood.
- Characterizing the tumor genomically.
Participants
The clinical trial focuses on evaluating the efficacy of tafasitamab and lenalidomide in combination with rituximab for patients diagnosed with **Diffuse Large B-Cell Lymphoma**. The study population includes both male and female participants aged 80 years and older, with a good general health status as indicated by an ECOG performance status of 2 or less. Participants must have a minimum life expectancy of three months and be able to receive the R-miniCHOP regimen. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are required to have histologically proven CD20+ diffuse large B-cell lymphoma, including various clinical subtypes, and must have previously untreated high-grade B-cell lymphoma. Lifestyle considerations such as the ability to receive adequate prophylaxis for thromboembolic events are relevant for inclusion. The trial population was selected based on specific inclusion criteria, including the requirement for a PET-positive disease and Ann Arbor stage I-IV. The sponsor has not disclosed the total number of participants involved in the study.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of a combination therapy involving **tafasitamab**, lenalidomide, and rituximab in patients aged 80 years or older with **Diffuse Large B-Cell Lymphoma**. This is a Phase II, open-label study, which means that both the researchers and participants know which treatment is being administered. The trial is expected to run from August 2021 to June 2027, with the primary objective being the assessment of the Overall Response Rate (ORR) after three cycles of treatment or at permanent treatment discontinuation, whichever occurs first.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on specific criteria, such as age, disease stage, and performance status. Following the screening, eligible participants will receive the study treatment, with follow-up visits scheduled to monitor response and safety. The end-of-study visit will occur after the completion of the treatment cycles or upon early termination. The expected length of participant involvement is approximately 10 months, although this may vary depending on individual response and tolerability.
Study visits are structured to ensure comprehensive monitoring and assessment of the treatment's efficacy and safety. The inclusion visit will involve informed consent and baseline assessments. Follow-up visits will include clinical evaluations, laboratory tests, and imaging studies to assess treatment response according to the Lugano Response Criteria. The end-of-study visit will involve final assessments and documentation of the participant's overall response and any adverse events.
Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. Additionally, any significant protocol deviations or non-compliance may also lead to early termination. The trial aims to provide valuable insights into the treatment's impact on overall survival, progression-free survival, and quality of life, while also assessing the safety profile of the combination therapy in this specific patient population.
Treatment
The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. The experimental medication **Tafasitamab** is provided as MINJUVI 200 mg powder for concentrate for solution for infusion. It is administered via **intravenous infusion**. The dosage is calculated based on body weight, with a maximum daily dose of 12 mg/kg and a total maximum dose of 288 mg/kg over a treatment period of up to 10 weeks. Participant compliance is monitored through regular assessments and infusion records.
**Lenalidomide** is administered as Zelvina 20 mg hard capsules, taken orally. The maximum daily dose is 20 mg, with a total maximum dose of 4.6 grams over a treatment period of up to 9 weeks. Compliance is monitored through pill counts and patient diaries.
**Rituximab** is provided in two formulations: MabThera 500 mg concentrate for solution for infusion and MabThera 1400 mg solution for subcutaneous injection. The intravenous formulation is administered with a maximum daily dose of 375 mg/m² and a total maximum dose of 2250 mg/m² over a 5-week period. The subcutaneous formulation is administered with a maximum daily dose of 1400 mg and a total maximum dose of 8.4 grams over the same period. Administration records and patient monitoring ensure compliance.
Non-experimental treatments include **Prednisone**, provided as PREDNISONE ARROW 20 mg tablets, administered orally or intravenously. The maximum daily dose is 60 mg/m², with a total maximum dose of 240 mg/m² over a 1-week period. **Vincristine sulfate** is administered as ONCOVIN 1 mg solution injectable via intravenous infusion, with a maximum daily and total dose of 1 mg over a 1-week period. **Cyclophosphamide** is administered as a powder for solution for injection/infusion, with a maximum daily and total dose of 400 mg/m² over a 1-week period. **Doxorubicin** is administered as a solution for infusion, with a maximum daily and total dose of 25 mg/m² over a 1-week period. **Vincristine** is also administered as a solution for injection, with a maximum daily and total dose of 1 mg over a 1-week period. Compliance for these treatments is monitored through administration records and patient assessments.
Efficacy
The efficacy of the treatment regimen in this clinical trial will be assessed primarily through the **Overall Response Rate (ORR)**, which includes patients achieving a Complete Metabolic Response or Partial Metabolic Response. This assessment will be based on investigator evaluations using the Lugano Response Criteria after three cycles of treatment or at the point of permanent treatment discontinuation, whichever occurs first. Secondary endpoints for efficacy evaluation include a central review of PET-CT scans according to the Lugano Response Criteria, Complete Metabolic Response rates based on both investigator and central assessments, Overall Survival, Quality of Life, and Progression-Free Survival. The safety of lenalidomide and tafasitamab in combination with rituximab will also be assessed as part of the secondary endpoints.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patient must understand and voluntarily sign an Informed Consent Form prior to any study-specific assessments/procedures being conducted
- Patient with histologically proven CD20+ diffuse large B-cell lymphoma (DLBCL) (WHO classification 2017) including all clinical subtypes (primary mediastinal, intravascular, etc…), with all IPI. May also be enrolled the following malignancies: • De Novo transformed DLBCL from low grade lymphoma (Follicular, other...) and DLBCL associated with some small cell infiltration in bone marrow or lymph node. • High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements • High-grade B-cell lymphoma, NOS • Follicular lymphoma grade 3B
- Positron-Emission Tomography (PET)-positive disease
- Previously untreated high-grade B-cell lymphoma
- Aged ≥ 80 years old at the time of signing the informed consent form (ICF)
- Ann Arbor stage I, II, III or IV
- ECOG performance status ≤ 2
- With a minimum life expectancy of 3 months
- Male patients must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for 4 months following study drug discontinuation, even if they have undergone a successful vasectomy
- Patients should be able to receive R-miniCHOP regimen (left ventricular ejection fraction > 50% and good general condition, according to investigator’s judgment)
- Patients should be able to receive adequate prophylaxis and/or therapy for thromboembolic events (aspirin or low molecular weight heparin)
- Patient covered by any social security system (France)
Exclusion Criteria
- Any other histological type of lymphoma, Burkitt included
- Any history of treated or non-treated Small-B cell lymphoma prior Aggressive B Cell lymphoma diagnosis
- Central nervous system or meningeal involvement by lymphoma
- Any serious active disease (according to the investigator’s decision)
- Poor renal function (calculated Cockcroft-Gault creatinine clearance < 30 ml/min)
- Poor hepatic function (total bilirubin level >30 μmol/l, transaminases >2.5 upper normal limits) unless these abnormalities are related to lymphoma
- Poor bone marrow reserve as defined by neutrophils <1G/L or platelets <100G/L, even if there is bone marrow infiltration by lymphoma. A Bone Marrow Aspiration will be mandatory prior inclusion for patients with neutrophils <1.5 G/L or Hemoglobin <9g/dL in order to exclude patients with concomitant myelodysplasia.
- Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma. Patients previously diagnosed with prostate cancer are eligible if (1) their disease was T1-T2a, N0, M0, with a Gleason score ≤7, and a prostate specific antigen (PSA) ≤10 ng/mL prior to initial therapy, (2) they had definitive curative therapy (i.e., prostatectomy or radiotherapy) 2 years before Day 1 of Cycle 1, and (3) at a minimum 2 years following therapy they had no clinical evidence of prostate cancer, and their PSA was undetectable if they underwent prostatectomy or <1 ng/mL if they did not undergo prostatectomy
- Treatment with any investigational drug within 30 days prior to prephase treatment and during the study
- Known HIV, active HCV infection or positive HBV test within 4 weeks before enrollment (except after hepatitis B vaccination or for patients who are HBs Ag negative, anti-HBs positive and/or anti-HBc positive but viral DNA negative)
- Prior treatment with anti-CD20/anti-CD19 monoclonal antibody or alemtuzumab within 3 months prior to prephase treatment
- Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide
- Contra-indication to highly dosed glucocorticoid (60 mg/m2/d)
- Neuropathy ≥ Grade 2 or painful
- Patient deprived of his/her liberty by a judicial or administrative decision
- Adult patient under legal protection
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 02 Aug 2021 | 8 |
 France | Not Recruiting | 02 Aug 2021 | 37 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
MabThera 500 mg concentrate for solution for infusion | Other | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 375 | 5 | PRD2154043 |
ONCOVIN 1 mg, solution injectable | Other | SOLUTION INJECTABLE | IV INFUSION | 1 | 1 | PRD515684 |
PREDNISONE ARROW 20 mg, comprimé sécable | Other | COMPRIMÉ SÉCABLE | ORAL AND IV | 60 | 1 | PRD1750631 |
CYCLOPHOSPHAMIDE | Other | — | INTRAVASCULAR USE | 400 | 1 | SUB06859MIG |
MINJUVI 200 mg powder for concentrate for solution for infusion | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 12 | 10 | PRD9171980 |
VINCRISTINE | Other | — | SOLUTION FOR INJECTION | 1 | 1 | SUB00059MIG |
DOXORUBICIN | Other | — | SOLUTION FOR INFUSION | 25 | 1 | SUB06391MIG |
Zelvina 20 mg hard capsules | Test | HARD CAPSULES | ORAL | 20 | 9 | PRD8721743 |
MabThera 1400 mg solution for subcutaneous injection | Other | SOLUTION FOR SUBCUTANEOUS INJECTION | SUBCUTANEOUS | 1400 | 5 | PRD1182393 |