Non-Hodgkin Lymphoma
Conditions
Brief summary
Pilot-trial of Methotrexate, Tafasitamab (Minjuvi®), Lenalidomide (Revlimid®) and Rituximab in patients ineligible for HCT-ASCT with Primary Central Nervous System Lymphoma (PCNSL)
Detailed description
This is a single-arm, prospective, multicenter, single-stage phase-II trial for patients aged 18-69 years with ECOG PS ≥2 or ≥70 years with previously untreated PCNSL, who are not eligible for HCT-ASCT at investigators decision. This trial evaluates the CRR rate after at least 2 cycles of MTR2, the incidence and severity of adverse events, progression-free survival, and overall survival after one year. It is planned to enroll eligible patients with PCNSL, i.e. who receive at least 2 cycles of the combination of rituximab, MTX and the IMPs tafasitamab and lenalidomide, over a one-year period. Follow-up will be conducted for 1 year within the trial.
Interventions
DRUGTafasitamab
IV
DRUGLenalidomide
Oral
DRUGRituximab
IV
DRUGMethotrexate
IV
Sponsors
Incyte Corporation
University of Cologne
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
single-arm, prospective, multicenter, single-stage phase-II trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-69 years with ECOG PS ≥2 or age ≥70 years, and ineligible for HCT-ASCT as per investigators discretion 2. Previously untreated, histologically (or cytologically) confirmed diagnosis of primary B-cell lymphoma of the central nervous system (PCNSL) by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy 3. At least one measurable lesion 4. Adequate organ function: * Adequate kidney function, defined as: * Serum creatinine estimated glomerular filtration rate (MDRD) ≥ 50 ml/min * Adequate hepatic function, defined as: * ALAT and ASAT ≤ 3 ULN * Bilirubin ≤ 2.0 mg/dl (except for Meulengracht disease) * Adequate bone marrow function, defined as: * White blood cell (WBC) count ≥ 3000/µL or absolute neutrophil count (ANC) ≥ 1000/µL * Platelets ≥ 50.000/µL * Hemoglobin \> 8.0 g/dl * Adequate cardiac function, defined as: * Cardiac ejection fraction ≥ 40% * Adequate pulmonary function as per investigators discretion 5. Written, signed, and dated informed consent for the trial provided by the participant 6. Female persons are eligible to participate if they are post-menopausal or females of no childbearing potential or if they agree to use a method of contraception considered safe described in Section 12.1.2.1. 7. Male persons with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods as described in Section 12.1.2.2.
Exclusion criteria
1. Prior treatment for PCNSL with the exception of a pre-phase treatment comprising steroid treatment and / or single application of rituximab 375 mg/m² and methotrexate 3.5 g/m² 2. Systemic lymphoma manifestation outside the CNS 3. Diagnosis of previous Non-Hodgkin lymphoma at any time 4. Primary vitreoretinal or leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord 5. HIV infection of any stage as determined by presence of anti-HIV antibodies (confirmatory test) and / or presence of RNA confirmed by PCR 6. Previous or concurrent malignancies with the following exceptions: * Surgically cured carcinoma in-situ * Other kinds of cancer without evidence of disease for at least 5 years 7. Hypersensitivity to study treatment or any component of the formulation 8. Stomatitis or gastrointestinal ulcerations preventing the use of methotrexate 9. Hepatitis B, hepatitis C or hepatitis E infection as determined by PCR 10. Severe active infection 11. Congenital or acquired immunodeficiency including previous organ transplantation 12. Pregnant or nursing (lactating) women. 13. Lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate their own wishes correspondingly 14. Non-compliance, for reasons including, but not limited to the following: 1. Increased alcohol consumption, drug dependency or substance abuse that would interfere with cooperation with requirements of the trial 2. Refusal of blood products during treatment 3. Any similar circumstances that appear to make protocol treatment or long-term follow-up impossible 15. Relationship of dependence or employer-employee relationship to the sponsor or the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| complete response rate (CRR) | At the end of cycle 2 (each cycle is 21 days) | The CRR will be determined by IRC and according to IPCG criteria. This endpoint reflects the proportion of patients who can potentially proceed to different consolidation or maintenance strategies to achieve durable responses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best overall response rate (BORR) | At the end of cycle 4 (each cycle is 21 days) | is defined as the rate of patients having achieved a CR or PR according to at least one post-baseline tumor assessment |
| Progression-free survival (PFS) | After 1 year | will be calculated for each patient as time between the start of treatment with MTR2 and the date of first progression, relapse or death or, in cases of continuing response, the date of the last documented follow-up (FU-CRF or written medical report). |
| Overall survival (OS) | After 1 year | will be calculated for each patient as time between the start of treatment with MTR2 and the date of death or the date of the last documented follow-up (FU-CRF or written medical report). |
| Incidence and severity of adverse events | during induction therapy | Incidence and severity of adverse events, including toxic deaths during induction therapy will be summarized based on CTCAE grades |
Countries
Germany
Contacts
Primary ContactPeter Borchmann, Prof. Dr. med.
Backup ContactJan Michel Heger, Dr. med.
Outcome results
None listed