Open-label, randomised trial to evaluate the efficacy and safety of MOR00208 with bendamustine versus rituximab with bendamustine in adult patients with a cancer of B cells, a type of white blood cell responsible for producing antibodies, which has returned after a period of improvement or that has proved resistant, or does not respond to, treatment
- Conditions
- Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL)MedDRA version: 19.0Level: PTClassification code 10012821Term: Diffuse large B-cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.0Level: PTClassification code 10012822Term: Diffuse large B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004689-11-RO
- Lead Sponsor
- MorphoSys AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 330
Diagnosis/Trial Population
1. Age =18 years
2. Histologically confirmed diagnosis of diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS); T cell/histiocyte rich large B-cell lymphoma (THRLBCL), Epstein-Barr virus (EBV) positive DLBCL of the elderly (EBV-positive DLBCL) 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. The only exception is the availability of tumour tissue acquired =3 years prior to Screening.
4. Patients must have:
a) R-R DLBCL
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 lesion must be positive on PET scan.
c) received at least one, but no more than three previous systemic therapy lines for the treatment of DLBCL and at least one therapy line must have included a CD20-targeted therapy (e.g. RTX)
d) Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
5. Patients after failure of ASCT or patients considered in the opinion of the investigator not eligible for salvage therapy including ASCT. Documentation of the reason for ineligibility for ASCT must be present 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 × 10E9/L (unless secondary to bone marrow involvement by DLBCL as demonstrated by bone marrow aspiration and bone marrow biopsy required for Screening)
b) platelet count =90 × 10E9/L (unless secondary to bone marrow involvement by DLBCL as demonstrated by bone marrow aspiration and bone marrow biopsy required for Screening) and absence of active bleeding
c) total serum bilirubin =2.5 × upper limit of normal (ULN) unless secondary to Gilbert’s syndrome (or pattern consistent with Gilbert’s) or documented liver involvement by lymphoma
d) ALT, AST and alkaline phosphatase (AP) =3 × ULN or <5 × ULN in cases of documented liver involvement by lymphoma
e) creatinine clearance must be =40 mL/min, calculated using a standard Cockcroft-Gault formula
7. For a female of childbearing potential (FCBP), a negative pregnancy test must be confirmed before enrolment. An FCBP must commit to take highly effective contraceptive precautions without interruption during the study and for 12 months after the last dose of study medication. An FCBP must refrain from breastfeeding and donating blood or oocytes during the course of the study and for 12 months after the last dose of study medication. Restrictions concerning blood donations apply as well to females who are not of childbearing potential.
8. If a male, an effective barrier method of contraception must be used without interruption during the study and for 6 months after the last dose of study medication if the patient is sexually active with an FCBP. Males must refrain from donating blood or sperm during the study participation and for 6 months after the last dose of study medication.
9. In the opinion of the investigator, the patients must:
a) be able to comply with all study-related procedures, medication use, and evaluations
b) be able to understand and give informed consent
c) not be considered to be potentially unreliable and/or n
Exclusionary Diagnosis Criteria
1. Patients who have:
a) any other histological type of lymphoma including, e.g., primary mediastinal (thymic) large B-cell (PMBL) or Burkitt’s lymphoma
b) primary refractory DLBCL
c) patients with known double/triple hit DLBCL genetics characterised by simultaneous detection of MYC with BCL2 and/or BCL6 translocation, as defined by fluorescence in situ hybridisation (FISH). MYC, BCL2, BCL6 testing prior to study enrolment is not required.
d) central nervous system (CNS) lymphoma involvement in present or past medical history
Exclusionary Previous and Current Treatment Criteria
2. Patients who had a major surgery less than 30 days prior to Day 1 dosing
3. 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) received live vaccines
c) required parenteral antimicrobial therapy for active, intercurrent infections
4. Patients who:
a) in the opinion of the investigator, have not recovered sufficiently from the adverse toxic effects of prior therapies, major surgeries or significant traumatic injuries
b) were previously treated with CD19-targeted therapy or BEN
c) have a history of previous severe allergic reactions to compounds of similar biological or chemical composition to MOR00208, RTX, murine proteins or BEN, or the excipients contained in the study drug formulations
d) have undergone ASCT within a period of =3 months prior to signing the ICF. Patients who have a more distant history of ASCT must exhibit full haematological recovery before enrolment into the study.
e) have undergone previous allogeneic stem cell transplantation
f) concurrently use other anticancer or experimental treatments
Exclusionary Medical History Criteria
5. Prior history of malignancies other than DLBCL, unless the patient has been free of the disease for =3 years prior to Screening. Exceptions to the =3-year time limit include 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)
6. 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) evidence of active, severe infections (e.g., tuberculosis [TB], opportunistic infections) or sepsis
d) a history or evidence of severely immunocompromised state
e) a history or evidence of severe hepatic impairment (total serum bilirubin > 3 mg/dL), jaundice unless secondary to liver involvement by lymphoma
f) a history or evidence of clinically significant cardiovascular, cerebrovascular, CNS and/or other disease that, in the investigator’s opinion, would preclude participation in the study or compromise the patient’s ability to give informed consent.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method