A phase II trial investigating Gemcitabine/Oxaliplatin/Rituximab with Tafasitamab (MOR208) for patients aggressive Lymphoma.

Phase 1

• Conditions: Malignant B-cell lymphoma; MedDRA version: 21.0Level: PTClassification code 10003903Term: B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002373-59-DE
• Lead Sponsor: niversity Medical Center of the Johannes Gutenberg University Mainz

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-07-21
• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

Subjects meeting all of the following criteria will be considered for enrollment to the trial:
- Histologically proven diagnosis of
a) diffuse large cell B-cell lymphoma, and other aggressive B-cell lymphomas according to the WHO 2016 revision (specified in detail in the protocol)
b) follicular lymphoma grade 3B and
c) transformed indolent B-cell lymphoma (not more than 20 % of the patient population) according to the WHO classification (central pathology review)
- Relapsed disease or refractory disease, at least one but no more than two prior treatment lines
- age = 18 years
- No curative option available (age = 65yr and/or HCT-CI Score > 2) or s.p. HDT
- At least 1 measurable tumor mass (>1.5 cm x >1.0 cm) or bone marrow infiltration
- Adequate bone marrow reserve:
a) Platelets of at least 100 000/µl
b) absolute neutrophil count of at least 1000/µl
- Adequate hepatic and renal function:
a) Alanine aminotransferase (ALT) <2.5 x upper limit of normal (ULN)
b) Aspartate aminotransferase (AST) <2.5 x upper limit of normal (ULN)
c) Total bilirubin <1.5 x upper limit of normal (ULN) unless related to lymphoma
- Measured or calculated eGFR >50 ml/min (institutional standard)
- Eastern Cooperative Oncology Group (ECOG) performance Status =2, unless tumor associated and expected to improve on treatment
- Signed informed consent
- Adequate contraception (if needed)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

- CNS involvement (brain MRI is required only in cases of clinically suspicious involvement)
- no adequate pretreatment (R-CHOP-like, or BR for initial indolent lymphoma)
- systemic treatment within last 6 weeks, steroids for bridging are allowed
- prior allogeneic transplantation prior anti CD19 CAR T-cell therapy or prior Tafasitamab therapy
- pregnant or breast-feeding women
- severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure (NYHA III-IV), uncontrolled diabetes mellitus, pulmonary fibrosis, uncontrolled hyperlipoproteinemia)
- Prolongation of QTc interval > 450 ms, demonstrated in electrocardiogramm (two separate or one in triplicate) or family history for Long QT-syndrome
- active uncontrolled infections
- HIV positivity
- Hepatitis C
- active Hepatitis B, patients with HBs-Ag positivity and no measurable HBV-DNA are eligible
- Medical or psychological condition that would not permit completion of the trial or signing of informed consent
- Diagnosed or treated for a malignancy other than NHL except:
a) adequately treated non-melanoma skin cancer
b) curatively treated in-situ cancer of the cervix
c) ductal carcinoma in situ (DCIS) of the breast
d) other solid tumors curatively treated with no evidence of disease for >2 years
e) prostate cancer with a life expectancy of more than 2 years
- Concurrent treatment with another investigational agent or within the last 6 weeks prior to treatment initiation. Concurrent participation in non-treatment studies is not excluded.
- Known intolerance to any of the study drugs or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Determination of the ORR in the experimental arm and comparison to historic results (Analysis will be based on Lugano -Criteria ).;Secondary Objective: Determination of CR-Rate, PFS, OS<br>ORR based on Cheson 2007-criteria<br>Determination of QoL (global QoL, physical functioning, Fatigue);Primary end point(s): ORR of the regimen within the first 8 treatment cycles.;Timepoint(s) of evaluation of this end point: Within 8 treatment cycles

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - ORR (Cheson 2007-criteria)<br>- Progression free survival (Lugano)<br>- Overall survival<br>- CR-Rate (Lugano)<br>- Best response (Lugano)<br>- Quality of Life measured with EORTC QLQ C30 and NHL-HG29 (global QoL, physical functioning, fatigue)<br>- ORR in separate GCB vs. non GCB-analysis is planned<br><br>Safety Endpoints: Safety and tolerability as measured by rate of AE, SAE compared between Arm A and B;Timepoint(s) of evaluation of this end point: The complete Remission after 1 year