Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL) MedDRA version: 18.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: MOR00208
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: no INN assigned
Current Sponsor code: MOR00208
Other descriptive name: MOR00208
Concentration un
Sponsors
MorphoSys AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18–80 years old 2. Histologically confirmed diagnosis of DLBCL (not otherwise specified [NOS]) according to the Revised European American Lymphoma/World Health Organization (REAL/WHO) classification. Patients with evidence of histological transformation to DLBCL from indolent NHL are also eligible. 3. Recent tumour tissue for central pathology review and correlative studies must be provided as an adjunct to participation in this study. The only exception is the availability of tumour tissue acquired =3 years prior to screening for this protocol 4. Patients must have: a) relapsed and/or refractory disease as defined in the protocol b) at least one bidimensionally measurable disease site. The lesion must have a greatest transverse diameter of =1.5 cm and greatest perpendicular diameter of =1.0 cm at baseline c) received at least one, but no more than two previous systemic regimens for the treatment of DLBCL and one therapy line must have included a CD20-targeted therapy (e.g. RTX) d) an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 5. Patients not considered in the opinion of the investigator eligible, or patients unwilling to undergo intensive salvage therapy including ASCT because of, but not limited to, advanced age, comorbidities, impossibility or, refusal to perform ASCT. Documentation of the reason for a patient's ineligibility must be provided in the patient’s source data. Laboratory values 6. Patients must meet the following laboratory criteria at screening: a) absolute neutrophil count (ANC) =1.5 × 109/L (unless secondary to bone marrow involvement by DLBCL as demonstrated by recent bone marrow aspiration and bone marrow biopsy) b) platelet count =90 × 109/L (unless secondary to bone marrow involvement by DLBCL as demonstrated by recent bone marrow aspiration and bone marrow biopsy) c) total serum bilirubin =2.5 × upper limit of normal (ULN) or =3 × ULN in cases of documented liver involvement d) alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP) =3 × ULN or <5 × ULN in cases of documented liver involvement e) serum creatinine clearance must be =60 mL/minute either measured or calculated using a standard Cockcroft and Gault formula (Cockroft and Gault, 1976) General Provisions 7. Females of childbearing potential (FCBP) must: a) not be pregnant as confirmed by a negative serum pregnancy test at screening and a medically supervised urine pregnancy test prior to starting study therapy b) refrain from breastfeeding and donating blood or oocytes during the course of the study and for 3 months after the last dose of study medication. Restrictions concerning blood donation apply as well to females who are not of childbearing potential. c) agree to ongoing pregnancy testing during the course of the study, and after study therapy has ended. This applies even if the patient practices complete and continued sexual abstinence d) commit to continued abstinence from heterosexual intercourse if it is in accordance with her lifestyle (which must be reviewed on a monthly basis) or agree to use and be able to comply with the use of effective double-barrier contraception without interruption during the study and for 3 months after the last dose of study medication 8. Males must use an effective barrier method of contraception without interruption, refrain from donating blood or sperm during the study participation and for 3 months after the last do
Exclusion criteria
Exclusion criteria: 1. Patients who have: a) any other histological type of lymphoma including primary mediastinal (thymic) large B-cell (PMBL) or Burkitt lymphoma b) primary refractory DLBCL or relapsed within period =3 months of prior CD20-targeted therapy (e.g. RTX) c) a history of "double/triple hit" DLBCL characterised by simultaneous detection of MYC with BCL2 and/or BCL6 translocation(s) defined by fluorescence in situ hybridisation. MYC, BCL2, BCL6 testing prior to study enrolment is not required Exclusionary Previous and current treatment 2. Patients who have, within 14 days prior to Day 1 dosing: a) not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy b) undergone major surgery or suffered from significant traumatic injury c) received live vaccines. d) required parenteral antimicrobial therapy for active, intercurrent infections 3. Patients who: a) have, in the opinion of the investigator, not recovered sufficiently from the adverse toxic effects of prior therapies b) were previously treated with CD19-targeted therapy or IMiDs® (e.g. thalidomide, LEN) c) have a history of hypersensitivity to compounds of similar biological or chemical composition to MOR00208, IMiDs® and/or the excipients contained in the study drug formulations d) have undergone ASCT within the period = 3 months prior to signing the informed consent form. Patients who have a more distant history of ASCT must exhibit full haematological recovery before enrolment into the study e) have undergone previous allogenic stem cell transplantation f) have a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or are at high risk for a thromboembolic event in the opinion of the investigator and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period g) concurrently use other anticancer or experimental treatments Exclusionary Patient’s medical history 4. Prior history of malignancies other than DLBCL, unless the patient has been free of the disease for =5 years prior to screening. Exceptions to the =5 year time limit include a history of the following: a) basal cell carcinoma of the skin b) squamous cell carcinoma of the skin c) carcinoma in situ of the cervix d) carcinoma in situ of the breast e) carcinoma in situ of the bladder f) incidental histological finding of prostate cancer (Tumour/Node/Metastasis [TNM] stage of T1a or T1b) 5. Patients with: a) positive hepatitis B and/or C serology. b) known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV) c) CNS lymphoma involvement –present or past medical history d) history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator’s opinion preclude participation in the study or compromise the patient’s ability to give informed consent. e) history or evidence of rare hereditary problems of galactoseintolerance, the Lapp lactase deficiency or glucose-galactose malabsorption f) gastrointestinal abnormalities including the inability to take oral medication, requiring intravenous alimentation, or prior surgical procedure affecting absorption
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the activity of a combination of LEN with MOR00208 in terms of objective response rate (ORR = complete response [CR] + partial response [PR]) in adult patients with R-R DLBCL.;Secondary Objective: 1.To determine the disease control rate (DCR = CR + PR + stable disease [SD]) 2.To determine the duration of response (DoR) 3.To determine the activity of a combination of LEN with MOR00208 in terms of progression-free survival (PFS) 4.To determine the overall survival (OS) 5.To determine time to progression (TTP) 6.To determine the time to next treatment (TTNT) 7.To determine the safety of LEN combined with MOR00208 assessed according to the frequency and severity of adverse events (AEs) 8.To assess the potential immunogenicity of MOR00208 9.To assess the pharmacokinetics (PK) of MOR00208 10.To make a preliminary evaluation of ORR, DCR, DoR, PFS, OS, TTP and TTNT in patients treated with a combination of LEN plus MOR00208 in cohorts with a “low risk”, “low-intermediate”, “high-intermediate” and “high” International Prognostic Index (IPI) For full list please refer to the protocol.;Primary end point(s): Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR)) ;Timepoint(s) of evaluation of this end point: after end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. DCR, DoR, PFS, OS, TTP and TTNT 2. Incidence and severity of AEs 3. Determination and characterisation of a potential anti-MOR00208 antibody formation 4. PK analysis of MOR00208 5. Absolute and percentage change from baseline in measurements of B-, T- and NK cell populations 6. Analysis of exploratory and diagnostic biomarkers (e.g. CD19, CD20, BCL2, and BCL6 expression, CD16 expression on NK cells, ADCC capacity, gene expression profiling for cell of origin subtyping and evaluation of AEs and ORR stratified by Fc?RIIIa and Fc?RIIa polymorphism) are planned to be investigated during the course of the study. ;Timepoint(s) of evaluation of this end point: After end of study | — |
Countries
Belgium, Czech Republic, France, Germany, Hungary, Italy, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Program Lead Oncology
MorphoSys AG
Outcome results
None listed