Open Label Study to Evaluate the Safety and Efficacy of Lenalidomide With MOR00208 in Patients With R-R DLBCL
- Conditions
- Diffuse Large B-cell Lymphoma
- Interventions
- Registration Number
- NCT02399085
- Lead Sponsor
- MorphoSys AG
- Brief Summary
This is a Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Lenalidomide Combined with MOR00208 in Participants with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL).
- Detailed Description
The aim of this single-arm, multicentre, open-label Phase II study is to evaluate the Lenalidomide (LEN) combined with Tafasitamab (MOR00208) in adult participants with DLBCL who had relapsed after or were refractory to at least one, but no more than three previous systemic regimens administered for the treatment of their DLBCL and who were not candidates for high-dose chemotherapy and subsequent Autologous stem cell transplants and were thus considered to have exhausted their therapeutic options. One prior therapy line had to include an anti-CD20 targeted therapy (e.g., rituximab \[RTX\]).
MOR00208 and LEN were administered for up to 12 cycles (28 days each), followed by MOR00208 monotherapy until progression, in participants with at least stable disease or a better response.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 81
-
Age >18 years
-
Histologically confirmed diagnosis of DLBCL
-
Tumour tissue for central pathology review and correlative studies had to be provided.
-
Participants must had:
- relapsed and/or refractory disease
- at least one bidimensionally measurable, PET positive disease site (transverse diameter of ≥1.5 cm and perpendicular diameter of ≥1.0 cm at baseline)
- received at least one, but no more than three previous systemic regimens for the treatment of DLBCL and one therapy line must had included a CD20-targeted therapy
- Eastern Cooperative Oncology Group 0 to 2
-
Participants were not considered in the opinion of the investigator eligible, or participants unwilling to undergo intensive salvage therapy including ASCT
-
Participants had to meet the following laboratory criteria at screening:
- absolute neutrophil count ≥1.5 × 10˄9/L
- platelet count ≥90 × 10˄9/L
- total serum bilirubin ≤2.5 × ULN or ≤5 × ULN in cases of Glibert's Syndrome or liver involvement by lymphoma
- alanine transaminase, aspartate aminotransferase and alkaline phosphatase ≤3 × ULN or <5 × ULN in cases of liver involvement
- serum creatinine clearance ≥60 mL/minute
-
Females of childbearing potential (FCBP) must:
- not be pregnant
- refrain from breastfeeding and donating blood or oocytes
- agreed to ongoing pregnancy testing
- committed to continued abstinence from heterosexual intercourse, or agree to use and be able to comply with the use of double-barrier contraception
-
Males (if sexually active with a FCBP) had to
- use an effective barrier method of contraception
- refrain from donating blood or sperm
-
In the opinion of the investigator the participants had to:
- be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events
- be able to understand, give written informed consent and comply with all study-related procedures, medication use, and evaluations
- had no history of noncompliance in relation to medical regimens or not be considered potentially unreliable and/or uncooperative
- be able to understand the reason for complying with the special conditions of the pregnancy prevention risk management plan and gave written acknowledgement of this.
Major
-
Participants who had:
- other histological type of lymphoma
- primary refractory DLBCL
- a history of "double/triple hit" genetics
-
Participants who had, within 14 days prior to Day 1 dosing:
- not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy
- underwent major surgery or suffered from significant traumatic injury
- received live vaccines.
- required parenteral antimicrobial therapy for active, intercurrent infections
-
Participants who:
- had, in the opinion of the investigator, not recovered sufficiently from the adverse toxic effects of prior therapies
- were previously treated with CD19-targeted therapy or immunomodulatory drugs (IMiDs)® (e.g., thalidomide, LEN)
- had a history of hypersensitivity to compounds of similar biological or chemical composition to MOR00208, IMiDs® and/or the excipients contained in the study drug formulations
- had undergone ASCT within the period ≤ 3 months prior to the signing of the Informed Consent Form. Patients who had a more distant history of ASCT had to exhibit full haematological recovery before enrolment into the study
- had undergone previous allogenic stem cell transplantation
- had a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or were at a high risk for a thromboembolic event in the opinion of the investigator and who were not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period
- concurrently used other anti-cancer or experimental treatments
-
Prior history of malignancies other than DLBCL, unless the participant had been free of the disease for ≥5 years prior to screening.
-
Participants with:
- positive hepatitis B and/or C serology.
- known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV)
- CNS lymphoma involvement
- history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator's opinion preclude participation in the study or compromised the participant's ability to give informed consent.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tafasitamab (MOR00208) + lenalidomide (LEN) Tafasitamab MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208. Tafasitamab (MOR00208) + lenalidomide (LEN) Lenalidomide MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
- Primary Outcome Measures
Name Time Method Number of Participants With Best Objective Response Rate (ORR) Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled ORR = complete response \[CR\] + partial response \[PR\]; Independent Radiology/Clinical Review Committee (IRC) Evaluation.
ORR after MOR00208 and Lenalidomide combination therapy assessed by the IRC evaluation.
ORR was defined as the number of participants of the total number of participants treated with MOR00208 + LEN with CR or PR as best response achieved at any time during the study.
- Secondary Outcome Measures
Name Time Method Duration of Response (DoR) by IRC Evaluation Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled DoR \[months\] = (date of assessment of tumor progression or death - date of assessment of first documented response of (CR or PR) + 1)/30.4375.
DoR by Investigator (INV) Evaluation Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled DoR \[months\] = (date of assessment of tumour progression or death - date of assessment of first documented response of (CR or PR) + 1)/30.4375.
Progression-free Survival (PFS) by IRC Evaluation Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled PFS time was defined as the time (in months) from the date of the first administration of any study drug to the date of tumor progression or death from any cause.
Overall Survival (OS) Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled OS was defined as the time from the date of the first administration of any study drug until death from any cause (documented by the date of death).
PFS by INV Evaluation Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled PFS time was defined as the time (in months) from the date of the first administration of any study drug to the date of tumor progression or death from any cause.
Serum Drug Levels of MOR00208 Cycle 1 Days 1, 4, 15 predose and 1 hr post-dose; Cycle 2 Days 1, 15 predose and 1 hr post-dose; Cycle 3 Days 1, 15 predose and 1 hr post-dose; Cycles 4, 5, 6, 7, 9, 11,13, 15, 17, 19, 21, 23 Day 1 predose; End of Treatment The pharmacokinetics (PK) profile of MOR00208 was investigated by quantifying serum drug levels at baseline and after repeated IV administrations for up to 24 treatment cycles using sparse sampling.
MOR00208 PK sample was taken pre-dose and 1 hour ± 10 min after the end of MOR00208 infusion for Cycle 1 to Cycle 23. MOR00208 PK sample (pre-dose only) were taken in odd numbered additional treatment cycles only (e.g., treatment Cycles 13, 15,17, 19, 21, 23).Number of Participants Who Developed Anti-MOR00208 Antibodies Baseline, Up to a maximum of 23 cycles. The Anti-MOR00208 Antibodies were investigated by quantifying serum drug levels at baseline and after repeated intravenous (IV) administrations planned for up to 24 treatment cycles using sparse sampling. Anti-MOR00208 antibody sample (pre-dose only) were taken in odd numbered additional treatment cycles only (e.g., treatment Cycles 13, 15,17, 19, 21,23).
Disease Control Rate (DCR) by IRC Evaluation Approximately 2.5 years after first participant enrolled DCR = CR + PR + SD (Stable disease); IRC Evaluation DCR was defined as the number of participants having CR, PR or SD based on the best objective response achieved at any time during the study.
DCR by INV Evaluation Approximately 2.5 years after first participant enrolled DCR = CR + PR + SD (Stable disease); IRC Evaluation DCR was defined as the number of participants having CR, PR or SD based on the best objective response achieved at any time during the study.
Time to Progression (TTP) by IRC Evaluation Approximately 2.5 years after first participant enrolled TTP is defined as the time from the first administration of any study drug until documented DLBCL progression or death as a result of lymphoma.
TTP by INV Evaluation Approximately 2.5 years after first participant enrolled TTP is defined as the time from the first administration of any study drug until documented DLBCL progression or death as a result of lymphoma.
Time to Next Treatment (TTNT) Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled Kaplan-Meier analysis of TTNT in FAS population. TTNT is defined as the time from the first administration of any study drug to the institution of next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity and participant preference) or death of any cause, whatever comes first.
Event-free Survival (EFS) by IRC Evaluation Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled EFS is defined as the time (in months) from the date of the first administration of any study drug to the date of tumour progression, first initiation of a new non-study anti-neoplastic therapy or death from any cause whichever comes first.
Number of Participants That Experienced Treatment-emergent Adverse Events (TEAEs) Approximately 6.5 years after first participant enrolled TEAEs are defined as any adverse event reported in the following time interval (including the lower and upper limits): date of first administration of study treatment; date of last administration of study treatment + 30 days, or if they are considered to be related to the study drug.
Severity of Treatment-emergent Adverse Events (TEAEs) Approximately 6.5 years after first participant enrolled Number of participants with Severity of TEAEs during MOR00208 and LEN combination therapy.
Trial Locations
- Locations (57)
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Szpital Wojewodzki Nr 1 im. Fryderyka Chopina w Rzeszowie
🇵🇱Rzeszow, Poland
Cancer Care - Torrance Memorial Physician Network
🇺🇸Redondo Beach, California, United States
St. Mary's Hospital And Regional Medical Center
🇺🇸Grand Junction, Colorado, United States
AZ Groeninge-Campus Maria's Voorzienigheid
🇧🇪Kortrijk, Belgium
Centre Hospitalier Universitaire (CHU) de Liege
🇧🇪Liege, Belgium
Clinique Universitaire de Mont Godinne
🇧🇪Yvoir, Belgium
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Universitatsklinikum Essen, Abteilung Haematologie
🇩🇪Essen, Germany
Charleston Hematology Oncology Associates
🇺🇸Charleston, South Carolina, United States
Tyler Hematology-Oncology
🇺🇸Tyler, Texas, United States
Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)
🇩🇪Frankfurt, Germany
Klinikum Nuernberg Nord Medizinische Klinik 5 Hamatologie
🇩🇪Nürnberg, Germany
Semmelweis Egyetem I. Sz. Belgyogyaszati Klinika-Semmelweis University
🇭🇺Budapest, Hungary
Universitaetsklinikum Wuerzburg
🇩🇪Würzburg, Germany
AOU Maggiore della Cartia
🇮🇹Novara, Italy
DEKK, Belgyogyaszati Klinika
🇭🇺Debrecen, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz (Kaposi Mor County Hospital)
🇭🇺Kaposvár, Hungary
Pratia MCM Krakow
🇵🇱Krakow, Poland
Tor Vergata University Department Of Hematology
🇮🇹Roma, Italy
Szpital Wojewodzk I w Opolu SP ZOZ Oddzial Hematologii i Onkologii Hematologicznej
🇵🇱Opole, Poland
Hospital Universitario Puerta de Hierro de Majadahonda
🇪🇸Madrid, Spain
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych w Poznaniu im. prof. Ludwika Bierkowskiego
🇵🇱Poznan, Poland
Royal Liverpool University Hospital - Liverpool University Hospitals NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Hospital Universitari Germans Trias i Pujol (HUGTP)
🇪🇸Badalona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Institut Catala D'Oncologia-Hospital Duran Y Reynals
🇪🇸Barcelona, Spain
Hospital Universitario Fundacion Jimenez Diaz Servicio de Hematologia Unidad de Linformas Oncohealth Institute
🇪🇸Madrid, Spain
Hospital Universitario Quiron Salud Madrid
🇪🇸Pozuelo De Alarcón, Spain
Hospital Universitario Virgen del Rocio, Hospital de la Mujer Servicio de Hematologia
🇪🇸Sevilla, Spain
Sarah Cannon Research Institute
🇬🇧London, United Kingdom
Azienda Ospedaliera Univerisitaria Policlinico Consorziale Di Bari UOC Ematologia con Trapianto
🇮🇹Bari, Italy
Ist.Ematologia E Oncologia Medica L.E A.Seragnoli Azienda Ospedaliero-Universitaria, Policlinico S.Orsola-Malpighi
🇮🇹Bologna, Italy
Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica
🇮🇹Firenze, Italy
Azienda Ospedaliero - Universitaria Policlinico di Modena Dip di Medicina Diagnostica, Clinica e di Sanità Pubblica
🇮🇹Modena, Italy
A .O. S. Maria della Misericordia
🇮🇹Perugia, Italy
Az Ospedaliera Santa Maria Facolta di Medicina e Chirurgia
🇮🇹Terni, Italy
A.O.U. Citta della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Centre Hospitalier Lyon-Sud (CHLS)
🇫🇷Lyon, France
CHU De Clermont Ferrand - Hopital Estaing Service Hematologie Clinique Et Thrapie Cellulaire
🇫🇷Clermont-Ferrand, France
Hopital Universitaire Necker Enfants Malades Service de Hematologie Adultes
🇫🇷Paris, France
Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren
🇫🇷Limoges, France
The Newcastle Hospitals NHS Foundation Trust
🇬🇧Newcastle, United Kingdom
Complejo Hospitalario de Navarra (CHN)
🇪🇸Pamplona, Spain
UCLA - David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
St. Joseph Mercy Hospital Cancer Care Center
🇺🇸Ypsilanti, Michigan, United States
Norwalk Hospital
🇺🇸Norwalk, Connecticut, United States
University Hospital Olomouc Hematoonkologicka klinika
🇨🇿Olomouc, Czechia
Klinikum Grosshadern-Klinikum Der Ludwig-Maximilian Universitaet Muenchen
🇩🇪Munich, Germany
National Institute of Oncology Hematological Department
🇭🇺Budapest, Hungary
The Royal Bournemouth & Christchurch Hospitals
🇬🇧Bournemouth, United Kingdom
Central Coast Medical Oncology Corporation
🇺🇸Santa Maria, California, United States
Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z Warmimsko
🇵🇱Olsztyn, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Klinika Nowotworow Ukladu Chlonnego Ul.
🇵🇱Warszawa, Poland
MTZ Clinical Research Sp. z o.o
🇵🇱Warszawa, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
🇵🇱Warsaw, Poland
ZNA Middelheim dep Klinische studies Hematologie
🇧🇪Antwerp, Belgium