Study of Fc-Optimized Anti-CD19 Antibody (MOR00208) to Treat Non-Hodgkin´s Lymphoma (NHL)

• ClinicalTrials.gov Identifier: NCT01685008
• Recruitment Status: Active, not recruiting
• First Posted: September 13, 2012
• Last Update Posted: June 27, 2019
• Sponsor: MorphoSys AG
• Information provided by (Responsible Party): MorphoSys AG

Study Description

Brief Summary:

This is an open-label, multicentre study to characterize the safety and preliminary efficacy of the human anti CD19 antibody MOR00208 in adult subjects with relapsed/refractory non-Hodgkin´s lymphoma (NHL) who have received at least 1 prior therapy containing rituximab (at least once).

Condition or disease	Intervention/treatment	Phase
Non-Hodgkin Lymphoma	Drug: MOR00208 (formerly Xmab 5574)	Phase 2

Detailed Description:

The study enrols patients from four different NHL subtypes: FL, DLBCL, MCL and other indolent NHL. The study will employ a two-stage design where the decision to further enrol any NHL subtype in stage 2 will depend on best responses after two or three cycles in stage 1.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 92 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IIa, Open-label, Multicenter Study of Single-Agent MOR00208, an Fc-optimized Anti-CD19 Antibody in Patients With Relapsed or Refractory Non-Hodgkin´s Lymphoma (NHL)
• Actual Study Start Date: April 23, 2013
• Estimated Primary Completion Date: February 2020
• Estimated Study Completion Date: February 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: MOR00208 (formerly Xmab5574); intravenous Infusion of MOR00208, Fc-Optimized Anti-CD19 Antibody	Drug: MOR00208 (formerly Xmab 5574); Other Name: MOR208

Outcome Measures

Primary Outcome Measures :

1. Overall response rate (ORR) [ Time Frame: up to 4 years ]
   Proportion of Patients with Complete Response (CR) or Partial Response (PR)

Secondary Outcome Measures :

1. Stable Disease (SD) Rate [ Time Frame: up to 4 years ]
   Proportion of Patients with Stable Disease
2. Duration of Response (DoR) [ Time Frame: up to 4 years ]
   Time from first CR or PR to first documentation of relapse/progression
3. Time to Progression (TTP) [ Time Frame: up to 4 years ]
   Time from first dosing until documentation of progression or death due to lymphoma
4. Progression-free Survival (PFS) [ Time Frame: up to 4 years ]
   Time from first dosing until progression or death due to any case

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. male or female patients ≥ 18 years of age.

2. histologically-confirmed diagnosis according to REAL/WHO classification, of the following B-cell lymphomas :

   1. FL
   2. MCL
   3. DLBCL
   4. Other indolent NHL (eg, MZL/MALT)
3. Patients' NHL must have progressed after at least 1 prior rituximab containing regimen.

4. one site of measurable disease by magnetic resonance imaging (MRI) or computed tomography (CT) scan defined as at least one lesion that measures at least 1.5 × 1.5 cm,

   Exception:

   For patients with MCL only, patients with nonmeasurable disease but evaluable sites (bone marrow, spleen, peripheral blood, gastrointestinal tract) can be enrolled.

5. Patients who have previously received an autologous stem cell transplantation must be at least 4 weeks post-transplant before study drug administration and must have exhibited a full haematological recovery
6. discontinued previous monoclonal antibody therapy (except rituximab) or radioimmunotherapy administration for at least 60 days before study drug administration.
7. off rituximab for at least 14 days before the screening visit and be confirmed to have either no response or have disease progression after rituximab treatment.
8. Patients with DLBCL had a positive [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) scan at baseline (Cheson response criteria)
9. Life expectancy of > 3 months.
10. ECOG performance status of < 3.

11. laboratory criteria at screening:

    1. Absolute neutrophil count (ANC) ≥ 1.0 (1000/mm3)
    2. Platelet count ≥ 75 × 109/L without previous transfusion within 10 days of first study drug administration
    3. Haemoglobin ≥ 8.0 g/dL (may have been transfused)
    4. Serum creatinine < 2.0 x upper limit of normal (ULN)
    5. Total bilirubin ≤ 2.0 × ULN
    6. Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
12. If a female of childbearing potential, a negative pregnancy test must be confirmed before enrolment and use of double-barrier contraception, oral contraceptive plus barrier contraceptive, or confirmation of having undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation.
13. If a male, an effective barrier method of contraception must be used during the study and for 3 months after the last dose if the patient is sexually active with a female of childbearing potential.
14. able to comply with all study-related procedures, medication use, and evaluations.
15. able understand and give written informed consent and comply with the study protocol.

Exclusion Criteria:

1. Previous treatment with cytotoxic chemotherapy, immunotherapy, radiotherapy or other lymphoma specific therapy within 14 days before the screening visit or patient has not recovered from side effects of previous lymphoma-specific therapy.
2. Treatment with a systemic investigational agent within 28 days before the screening visit.
3. Previous treatment with an anti-CD19 antibody or fragments
4. Previous allogenic stem cell transplantation.
5. Known or suspected hypersensitivity to the excipients contained in the study drug formulation.
6. Clinically significant cardiovascular disease or cardiac insufficiency,cardiomyopathy, preexisting clinically significant arrhythmia, acute myocardial infarction within 3 months of enrolment, angina pectoris within 3 months of enrolment.
7. Clinical or laboratory evidence of active hepatitis B or hepatitis C 8. History of HIV infection.

9. Any active systemic infection (viral, fungal, or bacterial) requiring active parenteral antibiotic therapy within 4 weeks of study drug administration.

10. Current treatment with immunosuppressive agents other than prescribed corticosteroids (not more than 10-mg prednisone equivalent).

11. Major surgery or radiation therapy within 4 weeks before first study drug administration.

12. Systemic diseases (cardiovascular, renal, hepatic, etc) that would prevent study treatment in the investigator's opinion.

13. History or clinical evidence of central nervous system (CNS), meningeal, or epidural disease, including brain metastasis.

14. Active treatment/chemotherapy for another primary malignancy within the past 5 years 15. Pregnancy or breastfeeding in women and women of childbearing potential not using an acceptable method of birth control.

16. History of noncompliance to medical regimens or patients who are considered potentially unreliable not cooperative

Contacts and Locations

Locations

United States, Connecticut

MorphoSys Research Site

Norwalk, Connecticut, United States, 06856

United States, New Jersey

MorphoSys Research Site

Hackensack, New Jersey, United States, 07601

United States, Ohio

Morphosys Research Site

Columbus, Ohio, United States, 43201

United States, Texas

Morphosys Research Site

Lubbock, Texas, United States, 79410

Belgium

MorphoSys Research Site

Brussels #1, Belgium

MorphoSys Research Site

Brussels #2, Belgium

MorphoSys Research Site

Edegem, Belgium

Germany

MorphoSys Research Site

Berlin, Germany

MorphoSys Research Site

Mainz, Germany

Morphosys Research Site

Ulm, Germany

Hungary

Morphosys Research Site

Budapest #1, Hungary

MorphoSys Research Site

Budapest #2, Hungary

Morphosys Research Site

Debrecen, Hungary

Italy

MorphoSys Research Site

Bologna, Italy

MorphoSys Research Site

Firenze, Italy

Morphosys

Genova, Italy

Morphosys Research Site

Modena, Italy

Morphosys Research Site

Novara, Italy

Poland

MorphoSys Research Site

Chorzów, Poland

Morphosys Research Site

Kraków, Poland

Morphosys Research Site

Lódz, Poland

MorphoSys Research Site

Slupsk, Poland

Spain

Morphosys Research Site

Madrid #1, Spain

Morphosys Research Site

Madrid #2, Spain

MorphoSys Research Site

Madrid #3, Spain

Morphosys Research Site

Sevilla, Spain

Sponsors and Collaborators

MorphoSys AG

Investigators

• Principal Investigator: Kristi Blum, MD; Ohio State University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jurczak W, Zinzani PL, Gaidano G, Goy A, Provencio M, Nagy Z, Robak T, Maddocks K, Buske C, Ambarkhane S, Winderlich M, Dirnberger-Hertweck M, Korolkiewicz R, Blum KA. Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Ann Oncol. 2018 May 1;29(5):1266-1272. doi: 10.1093/annonc/mdy056.

• Responsible Party: MorphoSys AG
• ClinicalTrials.gov Identifier: NCT01685008 History of Changes
• Other Study ID Numbers: MOR208C201; 2012-002659-41 ( EudraCT Number )
• First Posted: September 13, 2012
• Last Update Posted: June 27, 2019
• Last Verified: June 2019

Keywords provided by MorphoSys AG:

NHL; CD19; MOR208; MOR00208; Xmab5574; B-Cell Non-Hodgkin´s Lymphoma; Fc-optimized Anti-CD19 Antibody; Tafasitamab

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Antibodies; Immunoglobulins; Immunologic Factors; Physiological Effects of Drugs