Clinical trial NCT05583071: Methotrexate, Tafasitamab, Lenalidomide and Rituximab in Patients With PCNSL
Official title: Pilot-trial of Methotrexate, Tafasitamab (Minjuvi®), Lenalidomide (Revlimid®) and Rituximab in Patients Ineligible for HCT-ASCT With Primary Central Nervous System Lymphoma (PCNSL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-Hodgkin Lymphoma
Lead sponsor: University of Cologne
Sponsor class: OTHER
Collaborators: name: Incyte Corporation
First posted: 2022-10-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: single-arm, prospective, multicenter, single-stage phase-II trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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) ≥ 60 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 12.1.2.2.
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

Primary outcomes:
measure: complete response rate (CRR)
timeFrame: At the end of cycle 2 (each cycle is 21 days)
Secondary outcomes:
measure: Best overall response rate (BORR)
timeFrame: At the end of cycle 4 (each cycle is 21 days)
measure: Progression-free survival (PFS)
timeFrame: After 1 year
measure: Overall survival (OS)
timeFrame: After 1 year
measure: Incidence and severity of adverse events
timeFrame: during induction therapy
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
state: Baden-Würtemberg
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart - Katharienenhospital
state: Baden-Württemberg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
state: Hamurg
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein Westphalen
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Cologne
country: Germany
facility: University of Cologne
Study officials:
References: