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A Trial to Evaluate the Efficacy and Safety of MOR208 With Bendamustine (BEN) Versus Rituximab (RTX) With BEN in Adult Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

NCT02763319

Description:

The purpose of the study is to compare the safety and efficacy of MOR208 with BEN versus RTX with BEN in adult patients with relapsed of refractory DLBCL.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Trial to Evaluate the Efficacy and Safety of MOR208 With Bendamustine (BEN) Versus Rituximab (RTX) With BEN in Adult Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
  • Official Title: A Phase 2/3, Randomised, Multicentre Study of MOR208 With Bendamustine Versus Rituximab With Bendamustine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL) Who Are Not Eligible for High-Dose Chemotherapy (HDC) and Autologous Stem-Cell Transplantation (ASCT)

Clinical Trial IDs

  • ORG STUDY ID: MOR208C204
  • SECONDARY ID: 2014-004689-11
  • NCT ID: NCT02763319

Conditions

  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
Rituximab (RTX)Rituxan, Mab TheraRituximab and bendamustine
MOR208MOR208 and bendamustine
Bendamustine (BEN)Levact/TreandaMOR208 and bendamustine

Purpose

The purpose of the study is to compare the safety and efficacy of MOR208 with BEN versus RTX with BEN in adult patients with relapsed of refractory DLBCL.

Detailed Description

      This is a randomised, two-arm, multicentre, open-label phase II/III efficacy and safety study
      of MOR208 in combination with BEN versus RTX in combination with BEN given to adult patients
      who have relapsed after or are refractory to at least one but no more than three prior
      systemic therapies and have failed, or are not candidates for HDC and ASCT, and have thus
      exhausted their therapeutic options of demonstrated clinical benefit. At least one prior
      therapy line must have included a CD20-targeted therapy.
    

Trial Arms

NameTypeDescriptionInterventions
MOR208 and bendamustineExperimentalMOR208 and bendamustine
  • MOR208
  • Bendamustine (BEN)
Rituximab and bendamustineActive ComparatorRituximab and bendamustine
  • Rituximab (RTX)
  • Bendamustine (BEN)

Eligibility Criteria

        INCLUSION CRITERIA:

          1. Age ≥18 years

          2. Histologically confirmed diagnosis, according to the World Health Organization (WHO,
             2008) classification, of: DLBCL NOS, THRLBCL, EBV-positive DLBCL, composite lymphoma
             with a DLBCL component with a DLBCL relapse subsequent to DLBCL treatment, disease
             transformed from an earlier diagnosis of low grade lymphoma (i.e. an indolent
             pathology such as follicular lymphoma, marginal zone lymphoma) into DLBCL with a DLBCL
             relapse subsequent to DLBCL treatment.

          3. Fresh tumour tissue for central pathology review must be provided as an adjunct to
             participation in this study. Should it not be possible to obtain a fresh tumour tissue
             sample, archival paraffin embedded tumour tissue acquired ≤3 years prior to screening
             for this protocol must be available for this purpose.

          4. Patients must have:

               1. relapsed or refractory DLBCL

               2. 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

               3. received at least one, but no more than three previous systemic therapy lines for
                  the treatment of DLBCL. At least one previous therapy line must have included a
                  CD20-targeted.

               4. ECOG 0 to 2

          5. Patients after failure of ASCT or patients considered in the opinion of the
             investigator currently not eligible for HDC with subsequent ASCT.

          6. Patients must meet the following laboratory criteria at Screening:

               1. ANC ≥1.5 × 109/L (unless secondary to bone marrow involvement by DLBCL)

               2. PLTs ≥90 × 109/L (unless secondary to bone marrow involvement by DLBCL) and
                  absence of active bleeding

               3. total serum bilirubin ≤2.5 × ULN unless secondary to Gilbert's syndrome (or
                  pattern consistent with Gilbert's) or documented liver involvement by lymphoma.
                  Patients with Gilbert's syndrome or documented liver involvement by lymphoma may
                  be included if their total bilirubin is ≤5 x ULN

               4. ALT, AST and AP ≤3 × ULN or <5 × ULN in cases of documented liver involvement by
                  lymphoma

               5. serum creatinine ≤2.0 x ULN or creatinine clearance must be ≥40 mL/min calculated
                  using a standard Cockcroft-Gault formula (Cockroft & Gault, 1976)

          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 3, 6 or 12 months after the
             last dose of MOR00208, BEN or RTX respectively, whichever is later. An FCBP must
             refrain from breastfeeding and donating blood or oocytes during the course of the
             study and for 3, 6 or 12 months after the last dose of MOR00208, BEN or RTX
             respectively, whichever is later. Restrictions concerning blood donations apply as
             well to females who are not of childbearing potential.

          8. Males must use an effective barrier method of contraception without interruption
             during the study and for 3, 6 or 12 months after the last dose of MOR00208, BEN or RTX
             respectively, whichever is later, if the patient is sexually active with an FCBP.
             Males must refrain from donating blood or sperm during study participation and for 3,
             6 or 12 months after the last dose of MOR00208, BEN or RTX respectively, whichever is
             later.

          9. In the opinion of the investigator, the patients must:

               1. be able to comply with all study-related procedures, medication use, and
                  evaluations

               2. be able to understand and give informed consent

               3. not be considered to be potentially unreliable and/or not cooperative.

        EXCLUSION CRITERIA:

          1. Patients who have: any other histological type of lymphoma including, e.g., primary
             mediastinal (thymic) large B-cell lymphoma (PMBL) or Burkitt's lymphoma, primary
             refractory DLBCL, patients with known "double/triple hit" DLBCL genetics, CNS lymphoma
             involvement in present or past medical history

          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:

               1. not discontinued CD20-targeted therapy, chemotherapy, radiotherapy,
                  investigational anticancer therapy or other lymphoma-specific therapy

               2. received live vaccines

               3. required parenteral antimicrobial therapy for active, intercurrent systemic
                  infections

          4. Patients who:

               1. in the opinion of the investigator, have not recovered sufficiently from the
                  adverse toxic effects of prior therapies, major surgeries or significant
                  traumatic injuries

               2. were previously treated with CD19-targeted therapy or BEN

               3. 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

               4. have undergone ASCT within a period of ≤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.

               5. have undergone previous allogeneic stem cell transplantation

               6. concurrently use other anticancer or experimental treatments

          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:

               1. basal cell carcinoma of the skin

               2. squamous cell carcinoma of the skin

               3. carcinoma in situ of the cervix, breast and bladder

             f) incidental histological finding of prostate cancer (Tumour/Node/Metastasis [TNM]
             stage of T1a or T1b)

          6. Patients with:

               1. positive hepatitis B and/or C serology

               2. known seropositivity for or history of active viral infection with HIV

               3. evidence of active, severe uncontrolled systemic infections or sepsis

               4. a history or evidence of severely immunocompromised state

               5. a history or evidence of severe hepatic impairment (total serum bilirubin > 3
                  mg/dL), jaundice unless secondary to Gilbert's syndrome or documented liver
                  involvement by lymphoma

               6. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:From date of randomization until recurrence/disease progression, unacceptable toxicity, death or discontinuation for any other reason, whichever comes first assessed up to 4 yrs
Safety Issue:
Description:To determine the efficacy of a combination of MOR208 with BEN versus a combination of RTX with BEN in terms of progression-free survival (PFS) in adult patients with R-R DLBCL.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:From date of randomization assessed up to 4 yrs
Safety Issue:
Description:To determine efficacy
Measure:Duration of response (DoR)
Time Frame:From date of randomization assessed up to 4 yrs
Safety Issue:
Description:To determine efficacy
Measure:overall survival (OS)
Time Frame:From date of randomization assessed up to 4 yrs
Safety Issue:
Description:To determine efficacy
Measure:disease control rate (DCR)
Time Frame:From date of randomization assessed up to 4 yrs
Safety Issue:
Description:To determine efficacy
Measure:time to progression (TTP)
Time Frame:From date of randomization assessed up to 4 yrs
Safety Issue:
Description:To determine efficacy
Measure:time to next treatment (TTNT)
Time Frame:From date of randomization assessed up to 4 yrs
Safety Issue:
Description:To determine efficacy
Measure:Number of patients with adverse events
Time Frame:assessed up to 4 yrs
Safety Issue:
Description:Number of participants with treatment- and non-treatment related adverse events as assessed by CTCAE
Measure:quality of life (QoL)
Time Frame:assessed up to 4 yrs
Safety Issue:
Description:EORTC QLQ-C30 and EQ-5D-5L questionnaires will be used
Measure:Number of patients developing MOR208 antibodies
Time Frame:assessed up to 2 yrs
Safety Issue:
Description:
Measure:Maximum Plasma Concentration of MOR208 (Cmax)
Time Frame:assessed up to 2 yrs
Safety Issue:
Description:
Measure:Apparent trough concentration (Cpd) of MOR00208
Time Frame:assessed up to 2 yrs
Safety Issue:
Description:

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MorphoSys AG

Trial Keywords

  • Diffuse Large B-cell Lymphoma
  • bendamustine
  • rituximab
  • combination therapy
  • CD19 monoclonal antibody
  • transplant ineligible

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