Clinical trial NCT02399085: Open Label Study to Evaluate the Safety and Efficacy of Lenalidomide With MOR00208 in Patients With R-R DLBCL
Official title: A Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Lenalidomide Combined With MOR00208 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma
Keywords: DLBCL
Efficacy
MOR00208
Tafasitamab
lenalidomide
Lead sponsor: MorphoSys AG
Sponsor class: INDUSTRY
First posted: 2015-03-26
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Major Inclusion Criteria:

1. Age \>18 years
2. Histologically confirmed diagnosis of DLBCL
3. Tumour tissue for central pathology review and correlative studies had to be provided.
4. 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
5. Participants were not considered in the opinion of the investigator eligible, or participants unwilling to undergo intensive salvage therapy including ASCT
6. 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
7. 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
8. Males (if sexually active with a FCBP) had to

   * use an effective barrier method of contraception
   * refrain from donating blood or sperm
9. 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 Exclusion Criteria:

1. Participants who had:

   * other histological type of lymphoma
   * primary refractory DLBCL
   * a history of "double/triple hit" genetics
2. 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
3. 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
4. Prior history of malignancies other than DLBCL, unless the participant had been free of the disease for ≥5 years prior to screening.
5. 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.

Primary outcomes:
measure: Number of Participants With Best Objective Response Rate (ORR)
timeFrame: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
Secondary outcomes:
measure: Duration of Response (DoR) by IRC Evaluation
timeFrame: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
measure: DoR by Investigator (INV) Evaluation
timeFrame: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
measure: Progression-free Survival (PFS) by IRC Evaluation
timeFrame: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
measure: PFS by INV Evaluation
timeFrame: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
measure: Overall Survival (OS)
timeFrame: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
measure: Disease Control Rate (DCR) by IRC Evaluation
timeFrame: Approximately 2.5 years after first participant enrolled
measure: DCR by INV Evaluation
timeFrame: Approximately 2.5 years after first participant enrolled
measure: Time to Progression (TTP) by IRC Evaluation
timeFrame: Approximately 2.5 years after first participant enrolled
measure: TTP by INV Evaluation
timeFrame: Approximately 2.5 years after first participant enrolled
measure: Time to Next Treatment (TTNT)
timeFrame: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
measure: Event-free Survival (EFS) by IRC Evaluation
timeFrame: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
measure: Serum Drug Levels of MOR00208
timeFrame: 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
measure: Number of Participants Who Developed Anti-MOR00208 Antibodies
timeFrame: Baseline, Up to a maximum of 23 cycles.
measure: Number of Participants That Experienced Treatment-emergent Adverse Events (TEAEs)
timeFrame: Approximately 6.5 years after first participant enrolled
measure: Severity of Treatment-emergent Adverse Events (TEAEs)
timeFrame: Approximately 6.5 years after first participant enrolled
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA - David Geffen School of Medicine
state: California
city: Redondo Beach
country: United States
facility: Cancer Care - Torrance Memorial Physician Network
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Grand Junction
country: United States
facility: St. Mary's Hospital And Regional Medical Center
state: Colorado
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Ypsilanti
country: United States
facility: St. Joseph Mercy Hospital Cancer Care Center
state: Michigan
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates
state: South Carolina
city: Tyler
country: United States
facility: Tyler Hematology-Oncology
state: Texas
city: Antwerp
country: Belgium
facility: ZNA Middelheim dep Klinische studies Hematologie
city: Kortrijk
country: Belgium
facility: AZ Groeninge-Campus Maria's Voorzienigheid
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire (CHU) de Liege
city: Yvoir
country: Belgium
facility: Clinique Universitaire de Mont Godinne
city: Olomouc
country: Czechia
facility: University Hospital Olomouc Hematoonkologicka klinika
city: Clermont-Ferrand
country: France
facility: CHU De Clermont Ferrand - Hopital Estaing Service Hematologie Clinique Et Thrapie Cellulaire
city: Limoges
country: France
facility: Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren
city: Lyon
country: France
facility: Centre Hospitalier Lyon-Sud (CHLS)
city: Paris
country: France
facility: Hopital Universitaire Necker Enfants Malades Service de Hematologie Adultes
city: Essen
country: Germany
facility: Universitatsklinikum Essen, Abteilung Haematologie
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)
city: Munich
country: Germany
facility: Klinikum Grosshadern-Klinikum Der Ludwig-Maximilian Universitaet Muenchen
city: Nürnberg
country: Germany
facility: Klinikum Nuernberg Nord Medizinische Klinik 5 Hamatologie
city: Würzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Budapest
country: Hungary
facility: Semmelweis Egyetem I. Sz. Belgyogyaszati Klinika-Semmelweis University
city: Budapest
country: Hungary
facility: National Institute of Oncology Hematological Department
city: Debrecen
country: Hungary
facility: DEKK, Belgyogyaszati Klinika
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz (Kaposi Mor County Hospital)
city: Bari
country: Italy
facility: Azienda Ospedaliera Univerisitaria Policlinico Consorziale Di Bari UOC Ematologia con Trapianto
city: Bologna
country: Italy
facility: Ist.Ematologia E Oncologia Medica L.E A.Seragnoli Azienda Ospedaliero-Universitaria, Policlinico S.Orsola-Malpighi
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica
city: Modena
country: Italy
facility: Azienda Ospedaliero - Universitaria Policlinico di Modena Dip di Medicina Diagnostica, Clinica e di Sanità Pubblica
city: Novara
country: Italy
facility: AOU Maggiore della Cartia
city: Perugia
country: Italy
facility: A .O. S. Maria della Misericordia
city: Roma
country: Italy
facility: Tor Vergata University Department Of Hematology
city: Terni
country: Italy
facility: Az Ospedaliera Santa Maria Facolta di Medicina e Chirurgia
city: Torino
country: Italy
facility: A.O.U. Citta della Salute e della Scienza di Torino
city: Krakow
country: Poland
facility: Pratia MCM Krakow
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z Warmimsko
city: Opole
country: Poland
facility: Szpital Wojewodzk I w Opolu SP ZOZ Oddzial Hematologii i Onkologii Hematologicznej
city: Poznan
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych w Poznaniu im. prof. Ludwika Bierkowskiego
city: Rzeszow
country: Poland
facility: Szpital Wojewodzki Nr 1 im. Fryderyka Chopina w Rzeszowie
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
city: Warszawa
country: Poland
facility: MTZ Clinical Research Sp. z o.o
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Klinika Nowotworow Ukladu Chlonnego Ul.
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol (HUGTP)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Catala D'Oncologia-Hospital Duran Y Reynals
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz Servicio de Hematologia Unidad de Linformas Oncohealth Institute
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro de Majadahonda
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra (CHN)
city: Pozuelo De Alarcón
country: Spain
facility: Hospital Universitario Quiron Salud Madrid
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio, Hospital de la Mujer Servicio de Hematologia
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth & Christchurch Hospitals
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital - Liverpool University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Newcastle
country: United Kingdom
facility: The Newcastle Hospitals NHS Foundation Trust
Study officials:
affiliation: MorphoSys AG
name: Johannes Duell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Salles G, Duell J, Gonzalez Barca E, Tournilhac O, Jurczak W, Liberati AM, Nagy Z, Obr A, Gaidano G, Andre M, Kalakonda N, Dreyling M, Weirather J, Dirnberger-Hertweck M, Ambarkhane S, Fingerle-Rowson G, Maddocks K. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. Epub 2020 Jun 5.
citation: Duell J, Maddocks KJ, Gonzalez-Barca E, Jurczak W, Liberati AM, De Vos S, Nagy Z, Obr A, Gaidano G, Abrisqueta P, Kalakonda N, Andre M, Dreyling M, Menne T, Tournilhac O, Augustin M, Rosenwald A, Dirnberger-Hertweck M, Weirather J, Ambarkhane S, Salles G. Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Haematologica. 2021 Sep 1;106(9):2417-2426. doi: 10.3324/haematol.2020.275958.
citation: Duell J, Obr A, Augustin M, Endell J, Liu H, Geiger S, Silverman IM, Ambarkhane S, Rosenwald A. CD19 expression is maintained in DLBCL patients after treatment with tafasitamab plus lenalidomide in the L-MIND study. Leuk Lymphoma. 2022 Feb;63(2):468-472. doi: 10.1080/10428194.2021.1986219. Epub 2021 Nov 15. No abstract available.
citation: Cherng HJ, Westin JR. Broadening the MIND: Tafasitamab and Lenalidomide versus Synthetic Controls. Clin Cancer Res. 2022 Sep 15;28(18):3908-3910. doi: 10.1158/1078-0432.CCR-22-1626.
citation: Nowakowski GS, Yoon DH, Peters A, Mondello P, Joffe E, Fleury I, Greil R, Ku M, Marks R, Kim K, Zinzani PL, Trotman J, Huang D, Waltl EE, Winderlich M, Kurukulasuriya NC, Ambarkhane S, Hess G, Salles G. Improved Efficacy of Tafasitamab plus Lenalidomide versus Systemic Therapies for Relapsed/Refractory DLBCL: RE-MIND2, an Observational Retrospective Matched Cohort Study. Clin Cancer Res. 2022 Sep 15;28(18):4003-4017. doi: 10.1158/1078-0432.CCR-21-3648.
citation: Zinzani PL, Rodgers T, Marino D, Frezzato M, Barbui AM, Castellino C, Meli E, Fowler NH, Salles G, Feinberg B, Kurukulasuriya NC, Tillmanns S, Parche S, Dey D, Fingerle-Rowson G, Ambarkhane S, Winderlich M, Nowakowski GS. RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma. Clin Cancer Res. 2021 Nov 15;27(22):6124-6134. doi: 10.1158/1078-0432.CCR-21-1471. Epub 2021 Aug 25.