Clinical study to evaluate the safety and effectiveness of lenalidomide combined with MOR00208 in adult patients with diffuse large B cell lymphoma that has progressed after previous treatment

Phase 1

• Conditions: Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL); MedDRA version: 21.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-004688-19-DE
• Lead Sponsor: MorphoSys AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-07-29
• Last Update Posted: 23 May 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Age >18 years
2. Histologically confirmed diagnosis of DLBCL not otherwise specified (NOS); T cell/histiocyte rich large B-cell lymphoma (THRLBCL); Epstein-Barr virus (EBV) positive DLBCL of the elderly (EBV-positive DLBCL), Grade 3b Follicular Lymphoma, Composite lymphoma with a DLBCL component with a subsequent DLBCL relapse, according to the Revised European American Lymphoma/World Health Organization (REAL/WHO) classification. Additionally, patients with the evidence of histological transformation to DLBCL from an earlier diagnosis of low grade lymphoma (i.e. an indolent pathology such as follicular lymphoma,
marginal zone lymphoma, chronic lymphocytic leukemia) into DLBCL with a subsequent DLBCL relapse are also eligible.
3. Fresh tumour tissue for central pathology review and correlative studies must be provided as an adjunct to participation in this study.
Should it not be possible to obtain a fresh tumour tissue sample from the patient, archival paraffin embedded tumour tissue acquired =3 years prior to screening for this protocol must be available for this purpose.
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 The lesions must be positive on PET scan.
c) received at least one, but no more than three 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) unless secondary to Gilbert's syndrome or documented liver involvement by lymphoma. Patients with Gilbert's syndrome or with documented liver involvement by lymphoma may be included if their total bilirubin is =5 × ULN (see exclusion criterion 5g)
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

Exclusion Criteria

Exclusionary Diagnosis
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
c) a history of double/triple hit genetics 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 galactose intolerance, 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
g) history or evidence of severe hepatic impairment (total serum bilirubin > 3mg/dL), jaundice unless secondary to Gilbert's syndrome or documented liver involvement by lymphoma (see inclusion criterion 6c)

Study & Design

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