September 3, 2012
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September 13, 2012
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April 5, 2023
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November 7, 2023
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November 7, 2023
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April 23, 2013
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April 6, 2022 (Final data collection date for primary outcome measure)
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Overall Response Rate (ORR) [ Time Frame: From first dose until Follow-up Visit 12, up to 4.5 years ] Proportion of patients with Complete Remission (CR; disappearance of all evidence of disease) or Partial Remission (PR; regression of measurable disease and no new sites), assessed as per the 2007 International Working Group (IWG) response criteria by radiographic evaluations (CT, PET, MRI, or other).
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Overall response rate (ORR) [ Time Frame: 4 years ] ORR=CR (Complete Remission) + PR(Partial Remission)
Antitumor activity of MOR00208
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- Stable Disease (SD) Rate [ Time Frame: From first dose until Follow-up Visit 12, up to 4.5 years ]
Proportion of patients with Stable Disease (failure to attain CR/PR with no progressive disease)
- Duration of Response (DoR) [ Time Frame: From first dose until Follow-up Visit 12, up to 4.5 years ]
Time from first CR or PR to first documentation of relapse/progression (any new lesion or increase by ≥ 50% of previously identified site)
- Time to Progression (TTP) [ Time Frame: From first dose until Follow-up Visit 12, up to 4.5 years ]
Time from first dosing until documentation of progression or death due to lymphoma
- Progression-free Survival (PFS) [ Time Frame: From first dose until Follow-up Visit 12, up to 4.5 years ]
Time from first dosing until progression or death due to any case
- Incidence and Severity of Adverse Events (AEs) [ Time Frame: From first dose until 30 days after last dose of MOR00208, up to 8.5 years ]
Number of patients with treatment-emergent AEs rated Mild, Moderate, and Severe
- Number and Proportion of Patients Who Potentially Developed Anti-MOR00208 Antibodies and Semiquantitative Anti-MOR00208 Antibody Assessments [ Time Frame: From first dose until Follow-up Visit 3, up to 7 months ]
Number of patients with at least one positive (+ve) post-Baseline sample containing positive anti-MOR00208 antibodies; Baseline (pre-dose) sample has to be tested negative (-ve)
- Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of MOR00208 [ Time Frame: Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8) ]
The highest concentration of MOR00208 measured in serum
- PK Parameter: Time to Maximum Serum Concentration Observed (Tmax) of MOR00208 [ Time Frame: Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8) ]
The time to highest concentration of MOR00208 measured in serum
- PK Parameter: Apparent Trough Serum Concentration Before Dosing (Clast) of MOR00208 [ Time Frame: Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8) ]
The last quantifiable concentration from the first dose of MOR00208
- PK Parameter: Area Under the Concentration Curve From Dose Time Zero to the Time the Last Quantifiable Concentration is Observed (AUC[0-t]) of MOR00208 [ Time Frame: Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8) ]
Area under the concentration curve. The time curve from time zero (0) to the time that the last concentration above the lower limit of quantification (LLQ) is observed.
- PK Parameter: Area Under the Concentration Curve From Dose Time Zero to Infinity (AUC[0-inf]) of MOR00208 [ Time Frame: Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks]) ]
Area under the concentration curve. The time curve from time zero (0) to infinity (inf), where infinity is computed from AUC0-t + [Ct/λZ)]. Ct is calculated from the concentration at the last sampling time at which the sample is above LLQ.
- PK Parameter: Apparent Terminal Rate Constant (λz) of MOR00208 [ Time Frame: Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks]) ]
Apparent terminal rate constant calculated from the regression analysis (slope) from the log-transformed measured concentrations on the terminal phase of the time-point concentration curve
- PK Parameter: Apparent Terminal Half-life (t[1/2]) of MOR00208 [ Time Frame: Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks]) ]
Apparent terminal half-life calculated from ln(2)/λz
- PK Parameter: Total Body Clearance (CL) of MOR00208 [ Time Frame: Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks]) ]
Total body clearance calculated for single or multiple doses: dose(s)/AUC(0-inf)
- PK Parameter: Apparent Volume of Distribution (Vz) of MOR00208 [ Time Frame: Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks]) ]
Apparent volume of distribution during the terminal phase, calculated from dose/(AUC(0-inf)*λz)
- Absolute Change From Baseline in Measurements of B-cell Populations [ Time Frame: Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years) ]
Actual change from baseline will be summarized descriptively by visit for the pharmacodynamic parameter: B-cell populations
- Percent Change From Baseline in Measurements of B-cell Populations [ Time Frame: Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years) ]
Relative change from baseline will be summarized descriptively by visit for the pharmacodynamic parameter: B-cell populations
- Absolute Change From Baseline in Measurements of T-cell Populations [ Time Frame: Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years) ]
Actual change from baseline will be summarized descriptively by visit for the pharmacodynamic parameter: T-cell populations
- Percent Change From Baseline in Measurements of T-cell Populations [ Time Frame: Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years) ]
Relative change from baseline will be summarized descriptively by visit for the pharmacodynamic parameter: T-cell populations
- Absolute Change From Baseline in Measurements of NK Cell Populations [ Time Frame: Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years) ]
Actual change from baseline will be summarized descriptively by visit for the pharmacodynamic parameter: NK cell populations
- Percent Change From Baseline in Measurements of NK Cell Populations [ Time Frame: Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years) ]
Relative change from baseline will be summarized descriptively by visit for the pharmacodynamic parameter: NK cell populations
- Evaluation of AEs Stratified by Baseline CD19 Expression on Malignant Lymphoma Cells [ Time Frame: From first dose until 30 days after last dose of MOR00208, up to 8.5 years ]
Incidence of AEs as stratified by presence of CD19 on malignant lymphoma cells detected by tumor biopsy/aspirate during Screening
- Evaluation of ORR Stratified by Baseline CD19 Expression on Malignant Lymphoma Cells [ Time Frame: From first dose until Follow-up Visit 12, up to 4.5 years ]
The analysis of the primary endpoint (ORR) will additionally be stratified by presence of CD19 on malignant lymphoma cells detected by tumor biopsy/aspirate during Screening
- Evaluation of AEs Stratified by FcγRIIa Polymorphism [ Time Frame: From first dose until 30 days after last dose of MOR00208, up to 8.5 years ]
Incidence of AEs as stratified by FcγRIIa polymorphism subgroups (genotypes HH, HR, or RR)
- Evaluation of AEs Stratified by FcγRIIIa Polymorphism [ Time Frame: From first dose until 30 days after last dose of MOR00208, up to 8.5 years ]
Incidence of AEs as stratified by FcγRIIIa polymorphism subgroups (genotypes FF, FV, or VV)
- Evaluation of ORR Stratified by FcγRIIa Polymorphism [ Time Frame: From first dose until Follow-up Visit 12, up to 4.5 years ]
The analysis of the primary endpoint (ORR) will additionally be stratified by FcγRIIa polymorphism subgroups (genotypes HH, HR, or RR)
- Evaluation of ORR Stratified by FcγRIIIa Polymorphism [ Time Frame: From first dose until Follow-up Visit 12, up to 4.5 years ]
The analysis of the primary endpoint (ORR) will additionally be stratified by FcγRIIIa polymorphism subgroups (genotypes FF, FV, or VV)
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- 1. Patients response duration evaluation by hematology, bone marrow aspirated or biopsy, CT [ Time Frame: bi monthly, up to 48 months ]
- 2. Safety will be evaluated by assessing adverse events, clinical lab data and vital signs, ECG, physical exam [ Time Frame: weekly, up to 4 years ]
- 3. Pharmacokinetics of MOR00208 (Pharmacokinetic assessment comprises: Cmax, tmax, t1/2, CL [ Time Frame: weekly, up to 12 weeks; 0, 1, 4, 24 hours post dose ]
- 4. Number of patients who develop anti-MOR00208 antibodies as a measure of immunogenicity [ Time Frame: monthly up to 4 years ]
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Not Provided
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Not Provided
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Study of Fc-Optimized Anti-CD19 Antibody (MOR00208) to Treat Non-Hodgkin's Lymphoma (NHL)
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A Phase IIa, Open-label, Multicenter Study of Single-agent MOR00208, an Fc-optimized Anti-CD19 Antibody, in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
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This is an open-label, multicenter study to characterize the safety and efficacy of the human anti-CD19 antibody MOR00208 in adult patients with relapsed/refractory non-Hodgkin's lymphoma (NHL) who have received at least 1 prior therapy containing rituximab (at least once).
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The study enrols patients from four different NHL subtypes: follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and other indolent NHL (iNHL). 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.
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Interventional
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Phase 2
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Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
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Non-Hodgkin Lymphoma
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Drug: MOR00208 (formerly Xmab 5574)
Other Name: MOR208
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Experimental: MOR00208 (formerly Xmab5574)
intravenous Infusion of MOR00208, Fc-Optimized Anti-CD19 Antibody
Intervention: Drug: MOR00208 (formerly Xmab 5574)
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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.
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Completed
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92
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120
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April 6, 2022
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April 6, 2022 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
- Male or female patients ≥ 18 years of age.
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Histologically-confirmed diagnosis according to Revised European American Lymphoma/World Health Organization classification, of the following B-cell lymphomas:
- FL
- Other indolent NHL (eg, MZL/MALT)
- DLBCL
- MCL
- Patients' NHL must have progressed after at least 1 prior rituximab containing regimen.
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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.
- 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.
- Discontinued previous monoclonal antibody therapy (except rituximab) or radioimmunotherapy administration for at least 60 days before study drug administration.
- 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.
- Patients with DLBCL had a positive [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) scan at baseline (Cheson 2007 response criteria).
- Life expectancy of > 3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of < 3.
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Laboratory criteria at screening:
- Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
- Platelet count ≥ 75 × 10^9/L without previous transfusion within 10 days of first study drug administration
- Haemoglobin ≥ 8.0 g/dL (may have been transfused)
- Serum creatinine < 2.0 x upper limit of normal (ULN)
- Total bilirubin ≤ 2.0 × ULN
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
- If a female of childbearing potential, a negative pregnancy test must be confirmed before enrolment and use of double-barrier contraception or oral contraceptive plus barrier contraceptive must be used during the study and for 3 months after the last dose, or confirmation of having undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation.
- 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.
- Able to comply with all study-related procedures, medication use, and evaluations.
- Able to understand and give written informed consent and comply with the study protocol.
Exclusion Criteria:
- 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.
- Treatment with a systemic investigational agent within 28 days before the screening visit.
- Previous treatment with an anti-CD19 antibody or fragments.
- Previous allogenic stem cell transplantation.
- Known or suspected hypersensitivity to the excipients contained in the study drug formulation.
- 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.
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Patients with positive hepatitis serology:
Hepatitis B (HBV): Patients with positive serology for HBV defined as positivity for hepatitis B surface antigen (HBsAg) or total anti-hepatitis B core antibody (anti-HBc). Patients positive for anti-HBc may be included if HBV DNA is not detectable.
Hepatitis C (HCV): Patients positive HCV serology (defined as positive for anti-HCV antibody [anti-HCV]) unless HCV-ribonucleic acid (RNA) is confirmed negative.
- History of HIV infection.
- Any active systemic infection (viral, fungal, or bacterial) requiring active parenteral antibiotic therapy within 4 weeks of study drug administration.
- Current treatment with immunosuppressive agents other than prescribed corticosteroids (not more than 10-mg prednisone equivalent).
- Major surgery or radiation therapy within 4 weeks before first study drug administration.
- Systemic diseases (cardiovascular, renal, hepatic, etc) that would prevent study treatment in the investigator's opinion.
- History or clinical evidence of central nervous system (CNS), meningeal, or epidural disease, including brain metastasis.
- Active treatment/chemotherapy for another primary malignancy within the past 5 years (except for ductal breast cancer in situ, non-melanoma skin cancer, prostate cancer not requiring treatment, and cervical carcinoma in situ).
- Pregnancy or breastfeeding in women and women of childbearing potential not using an acceptable method of birth control.
- History of noncompliance to medical regimens or patients who are considered potentially unreliable not cooperative.
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Belgium, Germany, Hungary, Italy, Poland, Spain, United States
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NCT01685008
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MOR208C201 2012-002659-41 ( EudraCT Number )
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No
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Not Provided
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Not Provided
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MorphoSys AG
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Same as current
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MorphoSys AG
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Same as current
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Not Provided
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Not Provided
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MorphoSys AG
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October 2023
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