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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) (B-MIND)

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ClinicalTrials.gov Identifier: NCT02763319
Recruitment Status : Recruiting
First Posted : May 5, 2016
Last Update Posted : March 5, 2018
Sponsor:
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
MorphoSys AG

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma Drug: Rituximab (RTX) Drug: MOR208 Drug: Bendamustine (BEN) Phase 2 Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: Outcome assessor: blinding on treatment group
Primary Purpose: Treatment
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)
Study Start Date : June 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2022


Arm Intervention/treatment
Experimental: MOR208 and bendamustine
MOR208 and bendamustine
Drug: MOR208
MOR208: MOR208 dose: 12 mg/kg intravenously (IV)
Drug: Bendamustine (BEN)
Other Name: Levact/Treanda
Active Comparator: Rituximab and bendamustine
Rituximab and bendamustine
Drug: Rituximab (RTX)
Rituximab: Dose: 375 mg/m2 IV
Other Names:
  • Rituxan
  • Mab Thera
Drug: Bendamustine (BEN)
Other Name: Levact/Treanda



Primary Outcome Measures :
  1. 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 ]
    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 :
  1. Objective response rate (ORR) [ Time Frame: From date of randomization assessed up to 4 yrs ]
    To determine efficacy

  2. Duration of response (DoR) [ Time Frame: From date of randomization assessed up to 4 yrs ]
    To determine efficacy

  3. overall survival (OS) [ Time Frame: From date of randomization assessed up to 4 yrs ]
    To determine efficacy

  4. disease control rate (DCR) [ Time Frame: From date of randomization assessed up to 4 yrs ]
    To determine efficacy

  5. time to progression (TTP) [ Time Frame: From date of randomization assessed up to 4 yrs ]
    To determine efficacy

  6. time to next treatment (TTNT) [ Time Frame: From date of randomization assessed up to 4 yrs ]
    To determine efficacy

  7. Number of patients with adverse events [ Time Frame: assessed up to 4 yrs ]
    Number of participants with treatment- and non-treatment related adverse events as assessed by CTCAE

  8. quality of life (QoL) [ Time Frame: assessed up to 4 yrs ]
    EORTC QLQ-C30 and EQ-5D-5L questionnaires will be used

  9. Number of patients developing MOR208 antibodies [ Time Frame: assessed up to 2 yrs ]
  10. Maximum Plasma Concentration of MOR208 (Cmax) [ Time Frame: assessed up to 2 yrs ]
  11. Apparent trough concentration (Cpd) of MOR00208 [ Time Frame: assessed up to 2 yrs ]


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02763319


Contacts
Contact: Mariola Dymkowska, MD +49 89 89927 26589 mariola.dymkowska@external.morphosys.com

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Sponsors and Collaborators
MorphoSys AG
ICON Clinical Research
Investigators
Principal Investigator: Grzegorz Nowakowski, MD Mayo Clinic

Responsible Party: MorphoSys AG
ClinicalTrials.gov Identifier: NCT02763319     History of Changes
Other Study ID Numbers: MOR208C204
2014-004689-11 ( EudraCT Number )
First Posted: May 5, 2016    Key Record Dates
Last Update Posted: March 5, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by MorphoSys AG:
Diffuse Large B-cell Lymphoma
bendamustine
rituximab
combination therapy
CD19 monoclonal antibody
transplant ineligible

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action